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Griffin CD, Ezenwa VO, Cowie RH. Insights into the biology of the rat lungworm, Angiostrongylus cantonensis. Parasit Vectors 2025; 18:163. [PMID: 40307883 PMCID: PMC12042383 DOI: 10.1186/s13071-025-06790-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Accepted: 04/03/2025] [Indexed: 05/02/2025] Open
Abstract
Angiostrongylus cantonensis is a parasitic nematode with a complex life cycle involving rats as definitive hosts and gastropods as intermediate hosts. The parasite can infect other organisms, including humans, in which it causes neuroangiostrongyliasis, a globally emerging but neglected disease. This primer reviews the biology of A. cantonensis including its life cycle and development in its natural, accidental, and paratenic hosts, as well as its expanding geographic distribution. It then considers recent advances in A. cantonensis research followed by exploring areas that are ripe for further investigation into this fascinating parasite.
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Affiliation(s)
- Chasen D Griffin
- Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI, USA.
| | - Vanessa O Ezenwa
- Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA
- Odum School of Ecology, University of Georgia, Athens, GA, USA
- Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
| | - Robert H Cowie
- Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI, USA
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Schumacher PP, Ajendra J, Lenz B, Risch F, Ehrens A, Nieto-Pérez C, Koschel M, Aden T, Hoerauf A, Hübner MP. Major basic protein and eosinophil peroxidase support microfilariae motility inhibition by eosinophil ETosis. PLoS Negl Trop Dis 2025; 19:e0012889. [PMID: 40029883 PMCID: PMC11902130 DOI: 10.1371/journal.pntd.0012889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 03/12/2025] [Accepted: 02/01/2025] [Indexed: 03/14/2025] Open
Abstract
Eosinophils are a hallmark of filarial infections. They are primary effector cells and can attack filariae by releasing extracellular traps that contain toxic cationic proteins, such as eosinophil peroxidase and major basic protein. Previous studies demonstrated that the extracellular traps of eosinophils are induced by the microfilariae of Litomosoides sigmodontis and that they inhibit their motility. In this project, we aimed to investigate the role of these cationic proteins during the extracellular trap-mediated immobilization of microfilariae. Our results indicate that extracellular DNA traps from knockout mice that lack eosinophil peroxidase or major basic protein are significantly less able to immobilize and kill microfilariae. Accordingly, the addition of these cationic proteins to in vitro cultures inhibited microfilariae motility in a dose-dependent manner. Moreover, we examined eosinophils from the natural host, the cotton rat Sigmodon hispidus. While eosinophils of cotton rats release DNA after stimulation with PMA and zymosan, microfilariae did not trigger this effector function. Our work shows that eosinophil granule proteins impair the motility of microfilariae and indicate significant differences in the effector functions of eosinophils between the mouse model and the natural host. We hypothesize that the absence of DNA nets released by cotton rat eosinophils in response to microfilariae may explain the higher microfilarial load and longer patency of the natural host.
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Affiliation(s)
- Pia Philippa Schumacher
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Jesuthas Ajendra
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Benjamin Lenz
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Frederic Risch
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Alexandra Ehrens
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Celia Nieto-Pérez
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Marianne Koschel
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Tilman Aden
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Achim Hoerauf
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
| | - Marc P. Hübner
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
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Sasaki H, Miyata J, Kawana A, Fukunaga K. Antiviral roles of eosinophils in asthma and respiratory viral infection. FRONTIERS IN ALLERGY 2025; 6:1548338. [PMID: 40083723 PMCID: PMC11903450 DOI: 10.3389/falgy.2025.1548338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 02/07/2025] [Indexed: 03/16/2025] Open
Abstract
Eosinophils are immune cells that are crucial for the pathogenesis of allergic diseases, such as asthma. These cells play multifunctional roles in various situations, including infection. They are activated during viral infections and exert antiviral activity. Pattern recognition receptors, toll-like receptor 7 and retinoic acid inducible gene-I, are important for the recognition and capture of RNA viruses. In addition, intracellular granule proteins (eosinophil cationic protein and eosinophil-derived neurotoxin) and intracellular nitric oxide production inactivate and/or degrade RNA viruses. Interestingly, eosinophil-synthesizing specialized pro-resolving mediators possess antiviral properties that inhibit viral replication. Thus, eosinophils may play a protective role during respiratory virus infections. Notably, antiviral activities are impaired in patients with asthma, and eosinophil activities are perturbed in proportion with the severity of asthma. The exact roles of eosinophils in RNA virus (rhinovirus, respiratory syncytial virus, and influenza virus)-induced type 2 inflammation-based asthma exacerbation remain unclear. Our research demonstrates that interferons (IFN-α and IFN-γ) stimulate human eosinophils to upregulate antiviral molecules, including guanylate-binding proteins and tripartite motifs. Furthermore, IFN-γ specifically increases the expression of IL5RA, ICAM-1, and FCGR1A, potentially enhancing cellular responsiveness to IL-5, ICAM-1-mediated adhesion to rhinoviruses, and IgG-induced inflammatory responses, respectively. In this review, we have summarized the relationship between viral infections and asthma and the mechanisms underlying the development of antiviral functions of human and mouse eosinophils in vivo and in vitro.
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Affiliation(s)
- Hisashi Sasaki
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Jun Miyata
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Akihiko Kawana
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Koichi Fukunaga
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
- Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
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Rajamanickam A, Babu S. Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology. Pathogens 2025; 14:223. [PMID: 40137708 PMCID: PMC11945129 DOI: 10.3390/pathogens14030223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 03/29/2025] Open
Abstract
Lymphatic filariasis (LF), or elephantiasis, is a neglected tropical disease caused by filarial worms, primarily Wuchereria bancrofti, transmitted through mosquito bites. It often begins in childhood but may not show symptoms until later, leaving many individuals asymptomatic for long periods. LF disrupts the lymphatic system, causing severe swelling in the limbs and genitals, leading to deformities and disabilities. The World Health Organization estimates that around 51 million people are affected globally, with 36 million suffering from chronic conditions like lymphedema and hydrocele. In 2021, approximately 882.5 million people in 44 countries required preventive chemotherapy, making LF the second leading parasitic cause of disability, significantly impacting socioeconomic status. The immune response to filarial parasites is complex, involving both innate and adaptive immune cells. A key feature of LF immunology is the antigen-specific Th2 response, expansion of IL-10-producing CD4+ T cells, and a muted Th1 response. This T cell hypo-responsiveness is crucial for sustaining long-term infections with high parasite densities. While the correlates of protective immunity are not fully understood-due in part to a lack of suitable animal models-T cells, particularly CD4+ Th2 cells, and B cells, play essential roles in immune protection. Moreover, host immune responses contribute to the disease's pathological manifestations. A failure to induce T cell hypo-responsiveness can lead to exaggerated inflammatory conditions such as lymphedema, hydrocele, and elephantiasis. Filarial infections also induce bystander effects on various immune responses, impacting responses to other infectious agents. This intricate immune interplay offers valuable insights into the regulation of immune responses to chronic infections. This review explores recent immunological research on lymphatic filarial worms, highlighting their effects on both innate and adaptive immune responses in humans and the mechanisms underlying this neglected tropical disease.
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Affiliation(s)
- Anuradha Rajamanickam
- National Institute of Allergy and Infectious Diseases, National Institutes of Health—International Center for Excellence in Research, Chennai 600031, India;
| | - Subash Babu
- National Institute of Allergy and Infectious Diseases, National Institutes of Health—International Center for Excellence in Research, Chennai 600031, India;
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Bu X, Peng X, Huang L, Zhao Y, Jiao J, Zhu J, Chen J, Huang X, Zheng A, Qu H, Yao J. Effect of ectoparasite Ichthyophthirius multifiliis on the histopathology and gill and gut microbiota of goldfish ( Carassius auratus). Front Vet Sci 2025; 12:1539446. [PMID: 39968107 PMCID: PMC11834160 DOI: 10.3389/fvets.2025.1539446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Introduction The ectoparasite Ichthyophthirius multifiliis, is the pathogen of white spot disease in freshwater fish, which parasitizes on gills, fins, and skins of fish, causing tissue damage and death of host. However, whether it influences gill and gut microbiota is still unknow. Methods In this study, H&E staining was used to show the gill and gut histopathological characteristics of I. multifiliis-infected and uninfected goldfish (Carassius auratus). Meanwhile, 16S rRNA gene amplicon sequencing was conducted to analyze the difference of gill and gut microbiota between I. multifiliis-infected and uninfected goldfish. Results Histopathological examination revealed that I. multifiliis has induced significant damage to the gills of goldfish, characterized by lamellae fusion, cell hyperplasia, cell hyperaemia, inflammatory infiltration, necrosis and desquamation. 16S rRNA gene sequencing result showed that alpha and beta diversity of gill microbiota was significantly reduced in the I. multifiliis-infected group, while no significant changes were observed in gut microbiota. Genus Candidatus Megaira exhibited the highest relative abundance in the I. multifiliis-infected group. Meanwhile, the abundance of opportunistic pathogens Aeromonas and Achromobacter were increased in the intestines of I. multifiliis-infected goldfish. Discussion The increased presence of Candidatus Megaira may originate from within the cells of I. multifiliis. The increase of opportunistic pathogens Aeromonas and Achromobacter may pose a threat to the health of goldfish. In summary, this study laid a foundation for further research on the interaction between I. multifiliis and host microbiota.
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Affiliation(s)
- Xialian Bu
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Xianqi Peng
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Lei Huang
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Yu Zhao
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
| | - Jinbiao Jiao
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Jian Zhu
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
| | - Jing Chen
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Xiaohong Huang
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Aqin Zheng
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
| | - Huantao Qu
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
| | - Jiayun Yao
- Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes, Chinese Sturgeon Research Institute, China Three Gorges Corporation, Yichang, China
- Key Laboratory of Healthy Freshwater Aquaculture, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fish Health and Nutrition of Zhejiang Province, Key Laboratory of Fishery Environment and Aquatic Product Quality and Safety of Huzhou City, Zhejiang Institute of Freshwater Fisheries, Huzhou, China
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Domínguez‐Castanedo O, Gaspar‐Navarro J, Zúñiga‐Vega JJ. Does the Infestation by Trematode Parasites Influence Trade-Offs Between Somatic Condition and Male Reproductive Traits in a Viviparous Fish? JOURNAL OF FISH DISEASES 2025; 48:e14038. [PMID: 39552180 PMCID: PMC11706311 DOI: 10.1111/jfd.14038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/24/2024] [Accepted: 10/08/2024] [Indexed: 11/19/2024]
Abstract
Life history theory predicts that a trade-off may occur when an increased investment in one fitness component causes a reduced investment in another. Parasites generate changes in the optimal life history traits of organisms, causing compromises for their hosts. The objective of this research was to determine whether trematodes Clinostomum sp. and Uvulifer sp. inflict measurable damage on the males of the viviparous fish Poeciliopsis infans, generating trade-offs between somatic condition and reproductive traits (gonad mass and gonopodium length). We found (i) a negative relationship of large encysted metacercariae and non-encysted metacercariae on somatic condition. Interestingly, individuals with a higher parasite load had a worse body condition, but bigger gonads and longer gonopodium; and, (ii) a bond between small encysted metacercariae and non-encysted metacercariae with smaller gonopodia, only in fish with poorer somatic condition. The strongest correlation was given by the non-encysted metacercariae, probably due to mechanical damage during migration through the body cavity. We did not find any trade-off effects of Uvulifer sp. We consider that the statistical effects found on somatic condition can be attributed to a greater reproductive investment, generating energetic costs that compromise their defences against infection, allowing a greater parasite load.
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Affiliation(s)
- Omar Domínguez‐Castanedo
- Laboratorio de Ecología Evolutiva y Demografía Animal, Departamento de Ecología y Recursos Naturales, Facultad de CienciasUniversidad Nacional Autónoma de MéxicoMexico CityMexico
- Asociación Mexicana Para el Estudio y Conservación de CyprinodontiformesMexico CityMexico
| | - Jorge Gaspar‐Navarro
- Laboratorio de Sanidad Acuícola y Parasitología Molecular, Departamento El Hombre y Su AmbienteUniversidad Autónoma Metropolitana, Unidad XochimilcoMexico CityMexico
| | - J. Jaime Zúñiga‐Vega
- Laboratorio de Ecología Evolutiva y Demografía Animal, Departamento de Ecología y Recursos Naturales, Facultad de CienciasUniversidad Nacional Autónoma de MéxicoMexico CityMexico
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Chen J, Wei L, Deng CM, Xiong J, Chen SM, Lu D, Li ZH, Chen Y, Xiao J, Chen TW. A liver CT based nomogram to preoperatively predict lung metastasis secondary to hepatic alveolar echinococcosis. Eur J Radiol 2025; 183:111865. [PMID: 39644597 DOI: 10.1016/j.ejrad.2024.111865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 11/24/2024] [Accepted: 11/28/2024] [Indexed: 12/09/2024]
Abstract
PURPOSE To develop a nomogram based on liver CT and clinical features to preoperatively predict lung metastasis (LM) secondary to hepatic alveolar echinococcosis (HAE). METHODS A total of 291 consecutive HAE patients from Institution A undergoing preoperative abdominal contrast-enhanced CT and chest unenhanced CT were retrospectively reviewed, and were randomly divided into the training and internal validation sets at the 7:3 ratio. 82 consecutive patients from Institution B were enrolled as an external validation set. A nomogram was constructed based on the significant CT and clinical features of HAE from the training set selected by univariable and multivariable analyses to predict LM, and its predictive accuracy was assessed by area under the receiver operating characteristic curve (AUC) and Brier score. Decision-curve analysis was applied to evaluate the clinical effectiveness. This nomogram was verified in two independent validation sets. RESULTS Eosinophil (odds ratio [OR] = 9.60; 95 % confidence interval [CI]: 1.80-51.11), lesion size (OR = 1.02; 95 %CI: 1.01-1.04), and moderate-severe invasion of inferior vena cava (IVC) (OR = 5.57; 95 %CI: 1.82-17.10) were independently associated with LM (all P-values < 0.05). The nomogram based on the three independent predictors displayed AUCs of 0.875 (95 %CI, 0.824-0.927), 0.872 (95 %CI, 0.787-0.957) and 0.836 (95 %CI, 0.729-0.943), and Brier score of 0.105, 0.1 and 0.118 in the training, internal validation and external validation sets, respectively. Decision-curve analysis showed good clinical utility. CONCLUSION A nomogram based on eosinophil, lesion size and moderate-severe invasion of IVC showed good ability and accuracy for preoperative prediction of LM due to HAE.
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Affiliation(s)
- Jing Chen
- The First Clinical College of Jinan University, Guangzhou 510630, Guangdong, China; Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
| | - Li Wei
- Department of Radiology, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Chun-Mei Deng
- Department of Radiology, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Jing Xiong
- Department of Radiology, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Song-Mei Chen
- Department of Radiology, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Ding Lu
- Sichuan Provincial Center for Disease Control and Prevention, Chengdu 610044, Sichuan, China.
| | - Zhi-Hong Li
- Department of Hepato-biliary Surgery, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Yao Chen
- Department of Digestive Medical, Ganzi Hospital, West China Hospital of Sichuan University (Ganzi Tibetan Autonomous Prefecture People's Hospital), Ganzi 626000, Sichuan, China.
| | - Jun Xiao
- Department of Pulmonary and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
| | - Tian-Wu Chen
- The First Clinical College of Jinan University, Guangzhou 510630, Guangdong, China; Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
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Chen Y, Ni J, Li M, Hong Y, Zhu K, Hong R, Deng L, Li Z, Pu J, Yang T, Wang Y. Safety of dupilumab in Chinese pediatric patients aged 6 months and older: a prospective real-world study. Front Pediatr 2025; 12:1524962. [PMID: 39895989 PMCID: PMC11782127 DOI: 10.3389/fped.2024.1524962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 12/17/2024] [Indexed: 02/04/2025] Open
Abstract
Objective This study analyzes the occurrence and characteristics of adverse drug reactions (ADRs) of dupilumab in children in a real-world setting. It aims to enhance clinical practice and minimize medication safety risks in pediatric patients. Methods This prospective study included children receiving dupilumab in the hospital between January 2022 and December 2023. Information on ADRs was collected and univariate and multivariate analyses were employed to identify high-risk factors for the occurrence of adverse effects in dupilumab treatment. Results A total of 65 ADRs occurred in 1,103 treatments in 127 patients, with an incidence of 27.56% (35/127). A total of 62 patients aged 6 or below participated in this study, accounting for 48.82%. Univariate analysis showed that gender, age, duration of medication, frequency of dupilumab use were risk factors for the occurrence of adverse effects (P < 0.05). Multivariate logistic regression analysis showed that age [odds ratio [OR]: 0.071, 95% confidence interval [CI]: 0.012-0.433; P = 0.004] and frequency of dupilumab use (OR: 3.306, 95% CI: 1.078-10.135; P = 0.036) were risk factors for adverse effects. The outcomes of ADRs were improved in 10 cases (15.38%) and completely recovered in 55 cases (84.62%). Conclusion Dupilumab has a good safety profile in Chinese children aged 6 months to 18 years for up to 2 years of treatment, with most adverse reactions being mild to moderate, and no serious ocular adverse reactions were reported. Age and frequency of dupilumab use were risk factors for adverse effects. Younger age and higher frequency of dupilumab use were associated with higher odds of ADRs.
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Affiliation(s)
- Yanhua Chen
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Jiang Ni
- Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Ming Li
- Center for ADR Monitoring of Jiangsu, Nanjing, Jiangsu, China
| | - Yuan Hong
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Kouzhu Zhu
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Rong Hong
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Li Deng
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Zhijie Li
- Department of Dermatology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Jie Pu
- Department of Dermatology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Ting Yang
- Department of Dermatology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
| | - Yan Wang
- Department of Pharmacy, AffiliatedChildren’s Hospital of Jiangnan University (Wuxi Children’s Hospital), Wuxi, Jiangsu, China
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Fang J, Fang H, Guo P, Peng Y, Chen P. Strongyloides stercoralis combined with concurrent multiple pathogens infections in an immunosuppressed patient: a case report. Front Med (Lausanne) 2025; 11:1519065. [PMID: 39845824 PMCID: PMC11753413 DOI: 10.3389/fmed.2024.1519065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Background Strongyloides stercoralis is an opportunistic pathogenic parasite. Most individuals with normal immune function may not exhibit significant symptoms, and the signs are atypical, which can easily lead to missed diagnoses and delayed treatment. People with underlying diseases and weakened immunity are prone to develop severe conditions after infection with Strongyloides stercoralis. Case presentation We report an immunocompromised patient in whom the pathogen was initially not detectable using traditional parasitic detection techniques. However, Strongyloides stercoralis was identified in both the alveolar lavage fluid and blood through metagenomic next-generation sequencing. Subsequently, Strongyloides stercoralis was detected in the alveolar lavage fluid after multiple rounds of testing using traditional microscopic examination techniques. Based on the mNGS results and other examination findings, the patient was diagnosed with Strongyloides stercoralis in combination with concurrent multiple pathogens infections. After the combined drug therapy of Meropenem, Vancomycin, and Albendazole, the patient's condition was gradually brought under control. Conclusion This case demonstrates the advantage of integrating traditional detection methods with metagenomics next-generation sequencing technology in the etiological diagnosis of immunocompromised individuals. It is conducive to clarifying the etiological diagnosis of patients and thereby facilitating the timely initiation of corresponding treatments.
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Affiliation(s)
- Jingchun Fang
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Laboratory Medicine, Nansha Division, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huimin Fang
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Laboratory Medicine, Nansha Division, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Penghao Guo
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yaqin Peng
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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10
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Brown GP, Shine R, Rollins LA. Does a biological invasion modify host immune responses to parasite infection? ROYAL SOCIETY OPEN SCIENCE 2025; 12:240669. [PMID: 39816740 PMCID: PMC11732422 DOI: 10.1098/rsos.240669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 08/13/2024] [Accepted: 12/04/2024] [Indexed: 01/18/2025]
Abstract
Biological invasions can disrupt the close and longstanding coevolved relationships between host and parasites. At the same time, the shifting selective forces acting on demography during invasion can result in rapid evolution of traits in both host and parasite. Hosts at the invasion front may reduce investment into costly immune defences and redistribute those resources to other fitness-enhancing traits. Parasites at the invasion front may have reduced pathogenicity because traits that negatively impact host dispersal are left behind in the expanding range. The host's immune system is its primary arsenal in the coevolutionary 'arms race' with parasites. To assess the effects of invasion history on immune responses to parasite infection, we conducted a cross-infection experiment which paired common-garden reared cane toads and lungworm parasites originating from various sites in their invaded range across northern Australia. Infected toads had larger spleens and higher concentrations of eosinophils than did uninfected toads. Infected toads also exhibited lower bacteria-killing ability, perhaps reflecting a trade-off of resources towards defences that are more specifically anthelminthic. The impact of infection intensity on multiple immune measures differed among toads and parasites from different parts of the invasion trajectory, supporting the hypothesis that invasion has disrupted patterns of local adaptation.
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Affiliation(s)
- Gregory P. Brown
- School of Natural Sciences, Macquarie University, Sydney, NSW2109, Australia
| | - Richard Shine
- School of Natural Sciences, Macquarie University, Sydney, NSW2109, Australia
| | - Lee A. Rollins
- Evolution & Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, NSW2052, Australia
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11
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Freitas RMPD, Benvindo-Souza M, Sotero DF, Lopes ATDC, Santos MA, Nogueira ARA, Vieira TB, de Melo E Silva D. Non-invasive biomarkers for investigating urban metal exposure in neotropical bats. JOURNAL OF HAZARDOUS MATERIALS 2024; 480:136245. [PMID: 39490167 DOI: 10.1016/j.jhazmat.2024.136245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 10/01/2024] [Accepted: 10/20/2024] [Indexed: 11/05/2024]
Abstract
In urban centers, sewage treatment plants (STPs) serve as foraging and shelter areas for bats; however, they are sources of persistent pollutants that affect the health of these animals. This study aimed to investigate the impact of pollutants from an STP on the health of different species of neotropical bats from different guilds using non-invasive biomarkers. A conservation unit, the Silvania National Forest (SNF), was used as a reference area for comparison purposes. Blood, buccal mucosa, and fur samples were obtained for comet assay, micronucleus test, leukocyte profile, and metal concentration analysis in fur. Our results demonstrated that bats collected at the STP show a higher frequency of genotoxic damage, nuclear abnormalities, and an inflammatory response linked to infection than bats from the SNF. Regarding guilds, frugivores and nectarivores showed more pronounced responses to damage, but insectivores bats also showed relevant responses. While STPs are considered a source of pollutants, other urban sources of contamination likely contributed to these results. Still we encourage further studies using other non-invasive biomarkers, detection analysis of different pollutants in biological matrices, and the use of other wildlife species inserted in urban centers.
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Affiliation(s)
| | | | - Daiany Folador Sotero
- Laboratory of Mutagenesis, Institute of Biological Sciences (ICB I), Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Alice Tâmara de Carvalho Lopes
- Laboratory of Mutagenesis, Institute of Biological Sciences (ICB I), Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Mykaelli Andrade Santos
- Applied Instrumental Analysis Group, Department of Chemistry, Federal University of São Carlos, São Carlos, São Paulo, Brazil; Embrapa Pecuária Sudeste, São Carlos, São Paulo, Brazil
| | | | - Thiago Bernardi Vieira
- Laboratory of Ecology, Biological Sciences Faculty, Federal University of Pará, Altamira, Pará, Brazil
| | - Daniela de Melo E Silva
- Laboratory of Mutagenesis, Institute of Biological Sciences (ICB I), Federal University of Goiás, Goiânia, Goiás, Brazil
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12
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Gazzinelli-Guimaraes PH, Jones SM, Voehringer D, Mayer-Barber KD, Samarasinghe AE. Eosinophils as modulators of host defense during parasitic, fungal, bacterial, and viral infections. J Leukoc Biol 2024; 116:1301-1323. [PMID: 39136237 DOI: 10.1093/jleuko/qiae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 06/25/2024] [Indexed: 11/28/2024] Open
Abstract
Eosinophils, traditionally associated as central innate effector cells with type 2 immunity during allergic and helminth parasitic diseases, have recently been revealed to have important roles in tissue homeostasis as well as host defense in a broader variety of infectious diseases. In a dedicated session at the 2023 biennial conference of the International Eosinophil Society titled "Eosinophils in Host Defense," the multifaceted roles eosinophils play against diverse pathogens, ranging from parasites to fungi, bacteria, and viruses, were presented. In this review, the session speakers offer a comprehensive summary of recent discoveries across pathogen classes, positioning eosinophils as pivotal leukocytes in both host defense and pathology. By unraveling the intricacies of eosinophil engagement in host resistance, this exploration may provide valuable insights not only to understand specific underpinnings of eosinophil functions related to each class of pathogens but also to develop novel therapeutics effective against a broad spectrum of infectious diseases.
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Affiliation(s)
- Pedro H Gazzinelli-Guimaraes
- Department of Microbiology, Immunology and Tropical Medicine, The George Washington School of Medicine and Health Sciences, 2300 I Street NW, Washington, DC 20037, United States
| | - Shelby M Jones
- Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, United States
| | - David Voehringer
- Department of Infection Biology, Universitätsklinikum Erlangen, Wasserturmstrasse 3-5, 91054 Erlangen, Germany
- FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Katrin D Mayer-Barber
- Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD 20892, United States
| | - Amali E Samarasinghe
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Children's Foundation Research Institute, 50 N Dunlap Street, Memphis, TN 38103, United States
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13
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Walachowski S, Garo L, Sharma A, Jayaraman A, Noon J, Reinhardt C, Bosmann M. Disruption of the C5a/C5aR1 axis confers protection against hookworm infection in lung. Front Immunol 2024; 15:1475165. [PMID: 39628481 PMCID: PMC11611822 DOI: 10.3389/fimmu.2024.1475165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 10/23/2024] [Indexed: 12/06/2024] Open
Abstract
Hookworms are soil-transmitted parasitic nematodes that penetrate the host skin before migrating to the lungs. With an estimated 500-700 million people infected worldwide, hookworm infections are a neglected tropical disease and a significant cause of morbidity, particularly in children, pregnant women, and immunocompromised individuals. Although there is ample evidence that complement activation is pivotal to elicit a protective host immune response against invasive pathogens, its role in hookworm infection remains insufficiently explored. Here, we investigated the complement anaphylatoxin, C5a, during the early lung stage of infection with Nippostrongylus brasiliensis in C57BL/6J wild type and C5aR1-/- mice. Despite the previously reported ability of lung larvae to evade complement activation, C5a was detectable locally in lung tissue and bronchoalveolar lavages. Surprisingly, C5aR1 presence directly contributed to the pathogenicity of hookworm infection. The burden of viable parasites in the lungs was mitigated in C5aR1-/- mice, compared to C57BL/6J mice 48 hours post-infection. Additionally, C5aR1-/- mice showed significantly reduced lung injury, lower cytokine release, attenuated alveolar hemorrhage, and limited alveolar-capillary barrier disruption. Neutrophils were the most abundant and highest C5aR1-expressing cell type in the alveolar space after infection. Deficiency of C5aR1 reduced the influx of neutrophils, monocytes, and eosinophils to the pulmonary airways. RNA sequencing of alveolar neutrophils revealed C5aR1-dependent regulation of the novel nuclear protein, DEDD2. In conclusion, our findings highlight the impact of C5aR1 signaling in neutrophils during hookworm infection uncovering an unexpected downside of complement activation in parasitic infection.
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Affiliation(s)
- Sarah Walachowski
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Lucien Garo
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Arjun Sharma
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Mainz Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Archana Jayaraman
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Jason Noon
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Christoph Reinhardt
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Markus Bosmann
- Pulmonary Center, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
- Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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14
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Higham A, Beech A, Singh D. The relevance of eosinophils in chronic obstructive pulmonary disease: inflammation, microbiome, and clinical outcomes. J Leukoc Biol 2024; 116:927-946. [PMID: 38941350 DOI: 10.1093/jleuko/qiae153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 05/31/2024] [Accepted: 06/27/2024] [Indexed: 06/30/2024] Open
Abstract
Chronic obstructive pulmonary disease is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction, and poorly reversible airflow obstruction. A subgroup of patients with chronic obstructive pulmonary disease has higher blood eosinophil counts, associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 inflammation. Emerging evidence shows that patients with chronic obstructive pulmonary disease with increased pulmonary eosinophil counts have an altered airway microbiome. Higher blood eosinophil counts are also associated with increased lung function decline, implicating type 2 inflammation in progressive pathophysiology in chronic obstructive pulmonary disease. We provide a narrative review of the role of eosinophils and type 2 inflammation in the pathophysiology of chronic obstructive pulmonary disease, encompassing the lung microbiome, pharmacological targeting of type 2 pathways in chronic obstructive pulmonary disease, and the clinical use of blood eosinophil count as a chronic obstructive pulmonary disease biomarker.
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Affiliation(s)
- Andrew Higham
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and Manchester University NHS Foundation Trust, Manchester, M23 9LT, United Kingdom
| | - Augusta Beech
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and Manchester University NHS Foundation Trust, Manchester, M23 9LT, United Kingdom
| | - Dave Singh
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and Manchester University NHS Foundation Trust, Manchester, M23 9LT, United Kingdom
- Medicines Evaluation Unit, The Langley Building, Southmoor Road, Manchester, M23 9QZ, United Kingdom
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15
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FitzPatrick RD, Noone JR, Cartwright RA, Gatti DM, Brosschot TP, Lane JM, Jensen EL, Kroker Kimber I, Reynolds LA. Eosinophils respond to, but are not essential for control of an acute Salmonella enterica serovar Typhimurium infection in mice. Infect Immun 2024; 92:e0032524. [PMID: 39248486 PMCID: PMC11475665 DOI: 10.1128/iai.00325-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 09/10/2024] Open
Abstract
Eosinophils are a highly abundant cell type in the gastrointestinal tract during homeostatic conditions, where they have recently been reported to take on an activated phenotype following colonization by the bacterial microbiota. To date, there have been few studies investigating whether eosinophils respond to infection with enteric bacterial pathogens and/or investigating the requirements for eosinophils for effective bacterial pathogen control. In this study, we investigated the response of eosinophils to an acute enteric infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium. We also assessed whether eosinophil deficiency impacted Salmonella burdens in the intestinal tract or impacted the systemic dissemination of Salmonella following an oral infection of littermate wild-type BALB/cJ and eosinophil-deficient ΔdblGATA BALB/cJ mice. We found comparable Salmonella burdens in the intestinal tract of wild-type and eosinophil-deficient mice and no significant differences in the levels of Salmonella disseminating to systemic organs within 3 days of infection. Despite our evidence suggesting that eosinophils are not an essential cell type for controlling bacterial burdens in this acute infection setting, we found higher levels of eosinophils in gut-draining lymph nodes following infection, indicating that eosinophils do respond to Salmonella infection. Our data contribute to the growing evidence that eosinophils are responsive to bacterial stimuli, yet the influence of and requirements for eosinophils during bacterial infection appear to be highly context-dependent.
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Affiliation(s)
- Rachael D. FitzPatrick
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Jonathan R. Noone
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Richard A. Cartwright
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Dominique M. Gatti
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Tara P. Brosschot
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Jenna M. Lane
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Erik L. Jensen
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Isabella Kroker Kimber
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - Lisa A. Reynolds
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
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16
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Wang R, Lan C, Benlagha K, Camara NOS, Miller H, Kubo M, Heegaard S, Lee P, Yang L, Forsman H, Li X, Zhai Z, Liu C. The interaction of innate immune and adaptive immune system. MedComm (Beijing) 2024; 5:e714. [PMID: 39286776 PMCID: PMC11401974 DOI: 10.1002/mco2.714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 08/11/2024] [Accepted: 08/11/2024] [Indexed: 09/19/2024] Open
Abstract
The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune-related diseases, for example, the cGAS-STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single-cell sequencing technologies, CAR-T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.
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Affiliation(s)
- Ruyuan Wang
- Department of Thyroid and Breast Surgery Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
| | - Caini Lan
- Cancer Center Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
| | - Kamel Benlagha
- Alloimmunity, Autoimmunity and Transplantation Université de Paris, Institut de Recherche Saint-Louis, EMiLy, INSERM U1160 Paris France
| | - Niels Olsen Saraiva Camara
- Department of Immunology Institute of Biomedical Sciences University of São Paulo (USP) São Paulo São Paulo Brazil
| | - Heather Miller
- Coxiella Pathogenesis Section, Laboratory of Bacteriology Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health Hamilton Montana USA
| | - Masato Kubo
- Division of Molecular Pathology Research Institute for Biomedical Sciences (RIBS) Tokyo University of Science Noda Chiba Japan
| | - Steffen Heegaard
- Department of Ophthalmology Rigshospitalet Hospital Copenhagen University Copenhagen Denmark
| | - Pamela Lee
- Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China
| | - Lu Yang
- Department of Pathogen Biology School of Basic Medicine Tongji Medical College and State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology Wuhan Hubei China
| | - Huamei Forsman
- Department of Laboratory Medicine Institute of Biomedicine, University of Gothenburg Gothenburg Sweden
| | - Xingrui Li
- Department of Thyroid and Breast Surgery Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
| | - Zhimin Zhai
- Department of Hematology The Second Hospital of Anhui Medical University Hefei China
| | - Chaohong Liu
- Department of Pathogen Biology School of Basic Medicine Tongji Medical College and State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology Wuhan Hubei China
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17
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Yang Y, Xu L, Atkins C, Kuhlman L, Zhao J, Jeong JM, Wen Y, Moreno N, Kim KH, An YA, Wang F, Bynon S, Villani V, Gao B, Brombacher F, Harris R, Eltzschig HK, Jacobsen E, Ju C. Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury. Gut 2024; 73:1543-1553. [PMID: 38724220 PMCID: PMC11347249 DOI: 10.1136/gutjnl-2024-332033] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024]
Abstract
OBJECTIVE Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.
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Affiliation(s)
- Yang Yang
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Long Xu
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Constance Atkins
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Lily Kuhlman
- The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jie Zhao
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jong-Min Jeong
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Yankai Wen
- The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Nicolas Moreno
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kang Ho Kim
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Yu A An
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Fenfen Wang
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Steve Bynon
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Vincenzo Villani
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Bin Gao
- Laboratory of Liver Disease, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Frank Brombacher
- University of Cape Town Faculty of Health Sciences, Observatory, Western Cape, South Africa
| | - Raymond Harris
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Holger K Eltzschig
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Elizabeth Jacobsen
- Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Cynthia Ju
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
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18
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Wang H, Barry K, Zaini A, Coakley G, Moyat M, Daunt CP, Wickramasinghe LC, Azzoni R, Chatzis R, Yumnam B, Camberis M, Le Gros G, Perdijk O, Foong JPP, Bornstein JC, Marsland BJ, Harris NL. Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons. PLoS Pathog 2024; 20:e1011766. [PMID: 39141685 PMCID: PMC11346963 DOI: 10.1371/journal.ppat.1011766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 08/26/2024] [Accepted: 07/29/2024] [Indexed: 08/16/2024] Open
Abstract
Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether altered intestinal motility driven by the murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility, an observation that extended to another rodent nematode, Heligmosomoides polygyrus. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (<300 words).
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Affiliation(s)
- Haozhe Wang
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Kristian Barry
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Aidil Zaini
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Gillian Coakley
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Mati Moyat
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Carmel P. Daunt
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Lakshanie C. Wickramasinghe
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Rossana Azzoni
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Roxanne Chatzis
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Bibek Yumnam
- The Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
| | - Mali Camberis
- The Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
| | - Graham Le Gros
- The Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
| | - Olaf Perdijk
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Jaime P. P. Foong
- Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia
| | - Joel C. Bornstein
- Department of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia
| | - Benjamin J. Marsland
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
| | - Nicola L. Harris
- Department of Immunology, School of Translational Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
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19
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Chang LA, Schotsaert M. Ally, adversary, or arbitrator? The context-dependent role of eosinophils in vaccination for respiratory viruses and subsequent breakthrough infections. J Leukoc Biol 2024; 116:224-243. [PMID: 38289826 PMCID: PMC11288382 DOI: 10.1093/jleuko/qiae010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 12/12/2023] [Accepted: 12/26/2023] [Indexed: 02/01/2024] Open
Abstract
Eosinophils are a critical type of immune cell and central players in type 2 immunity. Existing literature suggests that eosinophils also can play a role in host antiviral responses, typically type 1 immune events, against multiple respiratory viruses, both directly through release of antiviral mediators and indirectly through activation of other effector cell types. One way to prime host immune responses toward effective antiviral responses is through vaccination, where typically a type 1-skewed immunity is desirable in the context of intracellular pathogens like respiratory viruses. In the realm of breakthrough respiratory viral infection in vaccinated hosts, an event in which virus can still establish productive infection despite preexisting immunity, eosinophils are most prominently known for their link to vaccine-associated enhanced respiratory disease upon natural respiratory syncytial virus infection. This was observed in a pediatric cohort during the 1960s following vaccination with formalin-inactivated respiratory syncytial virus. More recent research has unveiled additional roles of the eosinophil in respiratory viral infection and breakthrough infection. The specific contribution of eosinophils to the quality of vaccine responses, vaccine efficacy, and antiviral responses to infection in vaccinated hosts remains largely unexplored, especially regarding their potential roles in protection. On the basis of current findings, we will speculate upon the suggested function of eosinophils and consider the many potential ways by which eosinophils may exert protective and pathological effects in breakthrough infections. We will also discuss how to balance vaccine efficacy with eosinophil-related risks, as well as the use of eosinophils and their products as potential biomarkers of vaccine efficacy or adverse events.
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Affiliation(s)
- Lauren A Chang
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
| | - Michael Schotsaert
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1630, New York, NY 10029, United States
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
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20
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Hamad BS, Shnawa BH, Alrawi RA, Ahmed MH. Comparative analysis of host immune responses to Hydatid cyst in human and ovine hepatic cystic Echinococcosis. Vet Immunol Immunopathol 2024; 273:110775. [PMID: 38776648 DOI: 10.1016/j.vetimm.2024.110775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/08/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Hydatid disease is caused by the larval stages of the canine tapeworm Echinococcus granulosus. It is one of the most critical helminthic diseases, representing worldwide public health and socio-economic concern. AIM This study aimed to investigate the expression of apoptosis and immune response within hepatic tissues of humans and sheep infected with the Hydatid cyst. METHODS Paraffin-embedded tissue was prepared from each tissue sample and used for histopathological examination by Haematoxylin- Eosin. Also, toluidine blue staining was used for mast cell detection, while an immunohistochemical study was performed to assess CD3 T lymphocytes, CD4 helper T lymphocytes, CD8 cytotoxic T lymphocytes, CD20 memory B lymphocytes, CD68 macrophage, and caspase-3 antibodies. RESULTS The histological examination revealed significant changes, including the infiltration of inflammatory cells, predominantly lymphocytes with scattered giant cells, necrotic hepatic tissue, and fibrosis. Toluidine blue stain revealed a higher number of mast cells (5 cells/field) in humans compared to sheep (3.6 cells/field). The immunohistochemical analysis confirmed that the CD3 were the most predominant inflammatory cell in the hepatic tissue of humans (intensive 70%), and sheep (moderate 38.47%). Caspase-3 was observed in all samples in different grades and mostly in human liver tissue. CONCLUSION This data could aid in recognizing immunological markers for differentiating disease progression, as well as enhance the understanding of local immune responses to cystic Echinococcosis (CE). The findings could provide preliminary data for future studies on immune responses associated with Hydatid cysts.
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Affiliation(s)
- Bnar S Hamad
- Biology Department, Faculty of Science, Soran University, Soran, Kurdistan Region 30802, Iraq
| | - Bushra H Shnawa
- Biology Department, Faculty of Science, Soran University, Soran, Kurdistan Region 30802, Iraq
| | - Rafal A Alrawi
- Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq
| | - Mukhtar H Ahmed
- SISAF Drug Delivery Nanotechnology, Ulster University, Belfast BT37 0QB, UK.
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21
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Obeagu EI, Bluth MH. Eosinophils and Cognitive Impairment in Schizophrenia: A New Perspective. J Blood Med 2024; 15:227-237. [PMID: 38800637 PMCID: PMC11127652 DOI: 10.2147/jbm.s451988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 05/15/2024] [Indexed: 05/29/2024] Open
Abstract
Schizophrenia is a complex psychiatric disorder characterized by a wide array of cognitive impairments. While research has predominantly focused on the neurological aspects of schizophrenia, emerging evidence suggests that the immune system, specifically eosinophils, may play a significant role in the cognitive deficits associated with the disorder. This review presents a novel perspective on the interplay between eosinophils and cognitive impairment in schizophrenia. Eosinophils, traditionally associated with allergic responses and inflammation, have garnered limited attention within the realm of neuropsychiatry. Recent studies have hinted at a potential link between eosinophil activation and the pathogenesis of schizophrenia. In this comprehensive review, we delve into the world of eosinophils, elucidating their nature, functions, and interactions with the immune system. We examine the cognitive deficits observed in individuals with schizophrenia and discuss existing theories on the etiology of these impairments, focusing on immune system involvement. The paper also highlights the evolving body of research that supports the idea of eosinophilic influence on schizophrenia-related cognitive deficits. Furthermore, we explore potential mechanisms through which eosinophils may exert their effects on cognitive function in schizophrenia, including interactions with other immune cells and inflammatory pathways. By discussing the clinical implications and potential therapeutic avenues stemming from this newfound perspective, we underscore the practical significance of this emerging field of research. While this paper acknowledges the limitations and challenges inherent in studying eosinophils within the context of schizophrenia, it serves as a posit for novel thought in this vexing disease space as well as a call to action for future research endeavors. By providing a comprehensive survey of the existing literature and posing unanswered questions, we aim to inspire a reimagining of the relationship between eosinophils and cognitive impairment in schizophrenia, ultimately advancing our understanding and treatment of this debilitating disorder.
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Affiliation(s)
| | - Martin H Bluth
- Department of Pathology, Division of Blood Transfusion Medicine, Maimonides Medical Center, Brooklyn, NY, USA
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22
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Zhao D, Cheng T, Hu D, Xu X, Zhang F, Yu R, Li H, Wen P, Chen L, Fu M, Yang H, Zhang H, Yao J, Jin L. Maternal periodontal diseases affect the leukocyte profiles of umbilical cord blood: A cohort study. Oral Dis 2024; 30:2533-2545. [PMID: 37485723 DOI: 10.1111/odi.14683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/03/2023] [Accepted: 07/07/2023] [Indexed: 07/25/2023]
Abstract
AIM This study evaluated the connection of periodontal status with the leukocyte profiles of maternal peripheral blood (MPB) and umbilical cord blood (UCB). MATERIALS AND METHODS Ninety-nine pregnant females were recruited, and their data were collected via questionnaire and from medical records, including demographics, systemic conditions, complete blood count (CBC) and C-reaction protein (CRP) level in MPB. Full-mouth periodontal assessment was performed. CBC and CRP levels in UCB were measured after parturition. RESULTS All subjects and their neonates were generally healthy. 30.3% of the participants presented with periodontal health condition, whereas 69.7% had different severities of periodontal diseases. The counts/percentages of eosinophils and monocytes in UCB from the subjects with periodontal diseases elevated, and the percentage of neutrophils decreased referencing to that from the counterparts (p < 0.05). There were positive correlations for total leukocyte count, neutrophils and lymphocytes counts/percentages in MPB and UCB among the periodontally healthy subjects (r > 0.4, p < 0.05), but such findings did not exist in those with periodontal diseases. Moreover, periodontal diseases independently accounted for the counts/percentages of neutrophils and eosinophils in UCB after controlling confounders in four testing models (ANCOVA, p < 0.05). CONCLUSION Maternal periodontal diseases could to some extent disturb the leukocyte profiles of umbilical cord blood.
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Affiliation(s)
- Dan Zhao
- Department of Implant Dentistry, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
| | - Tianfan Cheng
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
| | - Dangli Hu
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China
| | - Xiaoyi Xu
- Division of Science & Education, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Feng Zhang
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Rong Yu
- Division of Science & Education, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Huijun Li
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Ping Wen
- Division of Science & Education, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Lihua Chen
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Mali Fu
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Hong Yang
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Hanyu Zhang
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Jilong Yao
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China
| | - Lijian Jin
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
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Abdel-Hakeem SS, Abdel-Samiee MAZ, Youssef MSE, Abd-Elsadek SH, Abd-Elrahman SM, Abdel-Hakeem SS. Nanocurcumin: A Promising Therapeutic Candidate for Experimental Trichinellosis. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2024; 30:368-381. [PMID: 38323506 DOI: 10.1093/micmic/ozae007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 12/18/2023] [Accepted: 01/18/2024] [Indexed: 02/08/2024]
Abstract
In our pursuit of an alternative drug against Trichinella spiralis, we assessed the effectiveness of nanocurcumin in alleviating pathogenesis, parasitological factors, MMP-9 levels, and its expression in the enteral and parenteral phases of infection. The nanocurcumin particles, with a spherical shape and a size of 100 ± 20 nm, were used in the study. Eighty mice were divided into four groups: the control group, the untreated infected group, the nanocurcumin-treated group, and the albendazole-treated group. The nanocurcumin-treated group exhibited a statistically significant increase in the percentage of lymphocytes, along with a reduction in neutrophils, monocytes, and eosinophils compared to the untreated, infected group. Both the nanocurcumin (87.2 and 97.3%) and the albendazole-treated groups (99.8 and 98.2%) showed a significant reduction in the mean number of intestinal worms and encysted larvae, respectively. The treated groups exhibited normal intestinal villi, suppression of the inflammatory process, and fewer instances of degenerated larvae in the diaphragm and muscle compared to the untreated, infected group. Immunohistochemistry and ELISA analyses revealed a significant downregulation of MMP-9 levels in the intestines and muscles of the treated groups. Our data demonstrate that nanocurcumin contains highly versatile molecules capable of modulating biological activity against inflammation and its pathway markers.
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Affiliation(s)
- Sara Salah Abdel-Hakeem
- Zoology and Entomology Department, Faculty of Science, Assiut University, Assiut 71526, Egypt
| | | | - Mohamed Salah Eldin Youssef
- Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt
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24
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Tanabe MB, Caravedo MA, Clinton White A, Cabada MM. An Update on the Pathogenesis of Fascioliasis: What Do We Know? Res Rep Trop Med 2024; 15:13-24. [PMID: 38371362 PMCID: PMC10874186 DOI: 10.2147/rrtm.s397138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 01/27/2024] [Indexed: 02/20/2024] Open
Abstract
Fasciola hepatica is a trematode parasite distributed worldwide. It is known to cause disease in mammals, producing significant economic loses to livestock industry and burden to human health. After ingestion, the parasites migrate through the liver and mature in the bile ducts. A better understanding of the parasite's immunopathogenesis would help to develop efficacious therapeutics and vaccines. Currently, much of our knowledge comes from in vitro and in vivo studies in animal models. Relatively little is known about the host-parasite interactions in humans. Here, we provide a narrative review of what is currently know about the pathogenesis and host immune responses to F. hepatica summarizing the evidence available from the multiple hosts that this parasite infects.
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Affiliation(s)
- Melinda B Tanabe
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Maria A Caravedo
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - A Clinton White
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
- Cusco Branch – Alexander von Humboldt Tropical Medicine Institute, Universidad Peruana Cayetano Heredia, Cusco, Peru
| | - Miguel M Cabada
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
- Cusco Branch – Alexander von Humboldt Tropical Medicine Institute, Universidad Peruana Cayetano Heredia, Cusco, Peru
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25
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Jesenak M, Diamant Z, Simon D, Tufvesson E, Seys SF, Mukherjee M, Lacy P, Vijverberg S, Slisz T, Sediva A, Simon HU, Striz I, Plevkova J, Schwarze J, Kosturiak R, Alexis NE, Untersmayr E, Vasakova MK, Knol E, Koenderman L. Eosinophils-from cradle to grave: An EAACI task force paper on new molecular insights and clinical functions of eosinophils and the clinical effects of targeted eosinophil depletion. Allergy 2023; 78:3077-3102. [PMID: 37702095 DOI: 10.1111/all.15884] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/21/2023] [Accepted: 08/27/2023] [Indexed: 09/14/2023]
Abstract
Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.
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Affiliation(s)
- Milos Jesenak
- Department of Clinical Immunology and Allergology, University Teaching Hospital in Martin, Martin, Slovak Republic
- Department of Paediatrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Teaching Hospital in Martin, Martin, Slovak Republic
- Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Teaching Hospital in Martin, Martin, Slovak Republic
| | - Zuzana Diamant
- Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden
- Department Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium
- Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
| | - Dagmar Simon
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ellen Tufvesson
- Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund University, Lund, Sweden
| | - Sven F Seys
- Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - Manali Mukherjee
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- The Firestone Institute for Respiratory Health, Research Institute of St. Joe's Hamilton, Hamilton, Ontario, Canada
| | - Paige Lacy
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Susanne Vijverberg
- Amsterdam UMC Location University of Amsterdam, Pulmonary Diseases, Amsterdam, The Netherlands
| | - Tomas Slisz
- Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
| | - Anna Sediva
- Department of Immunology, 2nd Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
| | - Ilja Striz
- Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jana Plevkova
- Department of Pathophysiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic
| | - Jurgen Schwarze
- Child Life and Health and Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Radovan Kosturiak
- Department of Paediatrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Teaching Hospital in Martin, Martin, Slovak Republic
- Outpatient Clinic for Clinical Immunology and Allergology, Nitra, Slovak Republic
| | - Neil E Alexis
- Center for Environmental Medicine, Asthma and Lung Biology, Department of Paediatrics, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Eva Untersmayr
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Martina Koziar Vasakova
- Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
| | - Edward Knol
- Department Center of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
- Department Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Leo Koenderman
- Department Center of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
- Department Pulmonary Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
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26
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Corewyn LC, Kelaita MA, Nollman J, Hagnauer I, Blanco-Peña K, Lessnau RG, Clayton JB, Shields-Cutler R, Stoos KB. Hematology and blood biochemistry in a declining population of mantled howler monkeys (Alouatta palliata palliata) at La Pacifica, Costa Rica. J Med Primatol 2023; 52:353-360. [PMID: 37655719 PMCID: PMC10841258 DOI: 10.1111/jmp.12669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 07/26/2023] [Accepted: 07/28/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Alouatta palliata palliata are an ecologically flexible howler monkey subspecies that has recently been relisted as Endangered. Populations are declining through much of the subspecies' range, including at our study site at La Pacifica, Costa Rica. Our objectives were to screen blood hematology and biochemistry samples collected from this wild population to elucidate their baseline health. METHODS We collected blood samples from 38 adult individuals from across the study site and analyzed 13 hematology and 14 biochemistry parameters. RESULTS Most hematology and blood biochemistry parameter values were similar between males and females. However, mean hemoglobin was significantly lower, and mean white blood cell count was significantly higher in females; and mean calcium and mean creatinine were significantly lower in females compared to males. CONCLUSIONS Overall, the La Pacifica population appeared healthy based on the blood parameters analyzed from sampled individuals. Our results were also largely consistent with published data available from other populations of A. p. palliata, and with reference values for captive Alouatta caraya.
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Affiliation(s)
- Lisa C Corewyn
- Department of Biology, Ithaca College, Ithaca, New York, USA
| | - Mary A Kelaita
- Department of Natural Sciences, St. Philip's College, San Antonio, Texas, USA
| | - Jenny Nollman
- The Cincinnati Zoo & Botanical Garden, Cincinnati, Ohio, USA
| | | | - Kinndle Blanco-Peña
- Instituto Regional de Estudios en Sustancias Tóxicas (IRET), Universidad Nacional, Costa Rica, Heredia, Costa Rica
| | | | - Jonathan B Clayton
- Department of Biology, University of Nebraska Omaha, Nebraska, Omaha, USA
- Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
- Primate Microbiome Project, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
| | | | - Kari Brossard Stoos
- Department of Health Sciences & Public Health, Ithaca College, Ithaca, New York, USA
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27
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Pera V, Brusselle GG, Riemann S, Kors JA, Van Mulligen EM, Parry R, de Wilde M, Rijnbeek PR, Verhamme KMC. Parasitic infections related to anti-type 2 immunity monoclonal antibodies: a disproportionality analysis in the food and drug administration's adverse event reporting system (FAERS). Front Pharmacol 2023; 14:1276340. [PMID: 38035014 PMCID: PMC10682182 DOI: 10.3389/fphar.2023.1276340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Methods: Spontaneous reports were used from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24-63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4-29.3). Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.
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Affiliation(s)
- Victor Pera
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Guy G. Brusselle
- Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
- Departments of Epidemiology and Respiratory Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Sebastian Riemann
- Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Jan A. Kors
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Erik M. Van Mulligen
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Rowan Parry
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Marcel de Wilde
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Peter R. Rijnbeek
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Katia M. C. Verhamme
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
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28
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Gazzinelli-Guimaraes PH, Golec DP, Karmele EP, Sciurba J, Bara-Garcia P, Hill T, Kang B, Bennuru S, Schwartzberg PL, Nutman TB. Eosinophil trafficking in allergen-mediated pulmonary inflammation relies on IL-13-driven CCL-11 and CCL-24 production by tissue fibroblasts and myeloid cells. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2023; 2:100131. [PMID: 37781651 PMCID: PMC10509988 DOI: 10.1016/j.jacig.2023.100131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 04/19/2023] [Accepted: 04/30/2023] [Indexed: 10/03/2023]
Abstract
Background The immunologic mechanisms underlying pulmonary type 2 inflammation, including the dynamics of eosinophil recruitment to the lungs, still need to be elucidated. Objective We sought to investigate how IL-13-producing TH2 effector cells trigger eosinophil migration in house dust mite (HDM)-driven allergic pulmonary inflammation. Methods Multiparameter and molecular profiling of murine lungs with HDM-induced allergy was investigated in the absence of IL-13 signaling by using IL-13Rα1-deficient mice and separately through adoptive transfer of CD4+ T cells from IL-5-deficient mice into TCRα-/- mice before allergic inflammation. Results We demonstrated through single-cell techniques that HDM-driven pulmonary inflammation displays a profile characterized by TH2 effector cell-induced IL-13-dominated eosinophilic inflammation. Using HDM-sensitized IL-13Rα1-/- mice, we found a marked reduction in the influx of eosinophils into the lungs along with a significant downregulation of both CCL-11 and CCL-24. We further found that eosinophil trafficking to the lung relies on production of IL-13-driven CCL-11 and CCL-24 by fibroblasts and Ly6C+ (so-called classical) monocytes. Moreover, this IL-13-mediated eotaxin-dependent eosinophil influx to the lung tissue required IL-5-induced eosinophilia. Finally, we demonstrated that this IL-13-driven eosinophil-dominated pulmonary inflammation was critical for limiting bystander lung transiting Ascaris parasites in a model of allergy and helminth interaction. Conclusion Our data suggest that IL-5-dependent allergen-specific TH2 effector cell response and subsequent signaling through the IL-13/IL-13Rα1 axis in fibroblasts and myeloid cells regulate the eotaxin-dependent recruitment of eosinophils to the lungs, with multiple downstream consequences, including bystander control of lung transiting parasitic helminths.
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Affiliation(s)
| | - Dominic P. Golec
- Laboratory of Immune System Biology, NIAID, National Institutes of Health, Bethesda, MD
| | - Erik P. Karmele
- Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, MD
| | - Joshua Sciurba
- Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD
| | - Pablo Bara-Garcia
- Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD
| | - Tom Hill
- National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Bioinformatics Resource, NIAID, National Institutes of Health, Bethesda, MD
| | - Byunghyun Kang
- Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, MD
| | - Sasisekhar Bennuru
- Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD
| | | | - Thomas B. Nutman
- Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD
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Chang MY, Brune JE, Black M, Altemeier WA, Frevert CW. Multicompartmental analysis of the murine pulmonary immune response by spectral flow cytometry. Am J Physiol Lung Cell Mol Physiol 2023; 325:L518-L535. [PMID: 37581225 PMCID: PMC10639014 DOI: 10.1152/ajplung.00317.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 07/12/2023] [Accepted: 07/24/2023] [Indexed: 08/16/2023] Open
Abstract
Studies of pulmonary inflammation require unique considerations due to the complex structure and composition of the lungs. The lungs have multiple compartments and diverse immune cell populations, with inherently high autofluorescence, and are involved in the host response to pulmonary pathogens. We describe a protocol that accounts for these factors through a novel combination of methodologies-in vivo compartmental analysis and spectral flow cytometry with a broad panel of antibodies. In vivo compartmental analysis enables the precise localization of immune cells within the marginated vasculature, lung interstitium, nonlavageable airways, and lavageable airways of the lungs, as well as the pulmonary lymph nodes. Spectral flow cytometry with a broad panel of antibodies supports an unbiased exploratory approach to investigating diverse immune cell populations during pulmonary inflammation. Most importantly, spectral flow uses cellular autofluorescence to aid in the resolution and identification of immune cell populations. This methodology enables the acquisition of high-quality data compatible with informed gating and dimensionality reduction algorithms. In addition, our protocol emphasizes considerations for compartmentalization of the inflammatory response, spectral flow panel design, and autofluorescence spectra analysis. These methodologies are critical for increasing the rigor of pulmonary research. We apply this protocol for the precise characterization and localization of leukocytes in the pulmonary host response to influenza A virus in C57BL/6J mice. In particular, we demonstrate that this protocol improves the quantification and localization of alveolar macrophages within the airways. The methodology is modifiable and expandable to allow for further characterization of leukocyte populations of special interest.NEW & NOTEWORTHY We describe a novel combination of methodologies that incorporates dual in vivo compartmental analysis using intravascular and intratracheal CD45 labeling, a broad panel of antibodies for identifying lymphoid and nonlymphoid cells, and spectral flow cytometry that uses cellular autofluorescence to aid in resolving and identifying immune cell populations. This methodology allows precise localization of immune cells in the lavageable airways, nonlavageable airways, interstitial lung tissue, and marginated in the lung vasculature.
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Affiliation(s)
- Mary Y Chang
- Department of Comparative Medicine, University of Washington, Seattle, Washington, United States
- Center for Lung Biology, University of Washington at South Lake Union, Seattle, Washington, United States
| | - Jourdan E Brune
- Department of Comparative Medicine, University of Washington, Seattle, Washington, United States
- Center for Lung Biology, University of Washington at South Lake Union, Seattle, Washington, United States
| | - Michele Black
- Department of Immunology, University of Washington, Seattle, Washington, United States
| | - William A Altemeier
- Center for Lung Biology, University of Washington at South Lake Union, Seattle, Washington, United States
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States
| | - Charles W Frevert
- Department of Comparative Medicine, University of Washington, Seattle, Washington, United States
- Center for Lung Biology, University of Washington at South Lake Union, Seattle, Washington, United States
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States
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30
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Cao Q, Wang R, Niu Z, Chen T, Azmi F, Read SA, Chen J, Lee VW, Zhou C, Julovi S, Huang Q, Wang YM, Starkey MR, Zheng G, Alexander SI, George J, Wang Y, Harris DC. Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury. JHEP Rep 2023; 5:100837. [PMID: 37691688 PMCID: PMC10482753 DOI: 10.1016/j.jhepr.2023.100837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 06/16/2023] [Accepted: 06/18/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND AND AIMS Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). METHODS ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. RESULTS Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. CONCLUSIONS This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. IMPACT AND IMPLICATIONS We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.
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Affiliation(s)
- Qi Cao
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Ruifeng Wang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
- Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, China
| | - Zhiguo Niu
- Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China
| | - Titi Chen
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Farhana Azmi
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Scott A. Read
- Storr Liver Centre, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Jianwei Chen
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Vincent W.S. Lee
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Chunze Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Sohel Julovi
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Qingsong Huang
- Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China
| | - Yuan Min Wang
- Centre for Kidney Research, Children’s Hospital at Westmead, Sydney, NSW, Australia
| | - Malcolm R. Starkey
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Guoping Zheng
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Stephen I. Alexander
- Centre for Kidney Research, Children’s Hospital at Westmead, Sydney, NSW, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Yiping Wang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - David C.H. Harris
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
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Murakami S, Uchida T, Imamura M, Suehiro Y, Namba M, Fujii Y, Uchikawa S, Teraoka Y, Fujino H, Ono A, Nakahara T, Murakami E, Okamoto W, Yamauchi M, Kawaoka T, Miki D, Hayes CN, Tsuge M, Ohira M, Ohdan H, Oka S. Correlation between serum pro-inflammatory cytokine levels and the prognosis of the patients with acute liver failure. J Gastroenterol Hepatol 2023; 38:1637-1646. [PMID: 37475200 DOI: 10.1111/jgh.16300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/31/2023] [Accepted: 07/02/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND AND AIM The prognosis of acute liver failure (ALF) remains poor, and liver transplantation is an alternative treatment option. Assessing the prognosis of ALF is important in determining treatment strategies. Here, we investigated clinical factors including serum pro-inflammatory cytokine levels that are associated with the prognosis of ALF. METHODS Sixty-six patients who developed ALF were enrolled in this study. Serum concentrations of 12 pro-inflammatory cytokines were measured on admission. The prognosis and factors associated with survival and development of hepatic coma were analyzed. RESULTS Of 66 patients, 4 patients underwent liver transplantation, and 49 patients were rescued without liver transplantation, while the remaining 13 patients died. Serum concentrations of interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-13, TNF, IFN -γ, IP-10, and G-CSF were significantly elevated in ALF patients. IL-4 and IL-8 levels were higher in patients who underwent liver transplantation or died than in rescued patients. Multivariable analysis identified age ≥ 55 years and IL-4 ≥ 1.2 pg/mL on admission as independent factors for mortality. Serum IL-8 levels were higher in patients with hepatic coma, and prothrombin-international normalized ratio ≥ 3.5 and IL-8 ≥ 77.2 pg/mL on admission were associated with development of hepatic coma after admission. CONCLUSION Serum levels of several pro-inflammatory cytokines were elevated in ALF patients. IL-4 and IL-8 were correlated with survival and development of hepatic coma after admission, respectively. Measurement of serum pro-inflammatory cytokines seems to be useful for the management of ALF.
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Affiliation(s)
- Serami Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takuro Uchida
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yosuke Suehiro
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Maiko Namba
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
- Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - C Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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Subsets of Eosinophils in Asthma, a Challenge for Precise Treatment. Int J Mol Sci 2023; 24:ijms24065716. [PMID: 36982789 PMCID: PMC10052006 DOI: 10.3390/ijms24065716] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/10/2023] [Accepted: 03/14/2023] [Indexed: 03/19/2023] Open
Abstract
The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term “eosinophils” was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of “LIAR” (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, “sine qua non”, for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.
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Xu L, Yang Y, Jiang J, Wen Y, Jeong JM, Emontzpohl C, Atkins CL, Kim K, Jacobsen EA, Wang H, Ju C. Eosinophils protect against acetaminophen-induced liver injury through cyclooxygenase-mediated IL-4/IL-13 production. Hepatology 2023; 77:456-465. [PMID: 35714036 PMCID: PMC9758273 DOI: 10.1002/hep.32609] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/31/2022] [Accepted: 06/01/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND AND AIMS A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated. APPROACH AND RESULTS In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality rate in WT mice. Mechanistic studies using eosinophil-specific IL-4/IL-13 knockout mice demonstrated that these cytokines, through inhibiting interferon-γ, mediated the hepatoprotective function of eosinophils. Reverse phase protein array analyses and in vitro experiments using various inhibitors demonstrated that IL-33 stimulation of eosinophils activated p38 mitogen-activated protein kinase (MAPK), and in turn, cyclooxygenases (COX), which triggered NF-κB-mediated IL-4/IL-13 production. In vivo adoptive transfer experiments showed that in contrast to naive eosinophils, those pretreated with COX inhibitors failed to attenuate AILI. CONCLUSIONS The current study revealed that eosinophil-derived IL-4/IL-13 accounted for the hepatoprotective effect of eosinophils during AILI. The data demonstrated that the p38 MAPK/COX/NF-κB signaling cascade played a critical role in inducing IL-4/IL-13 production by eosinophils in response to IL-33.
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Affiliation(s)
- Long Xu
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
- School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, China
| | - Yang Yang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jiali Jiang
- School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, China
| | - Yankai Wen
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jong-Min Jeong
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Christoph Emontzpohl
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Constance L. Atkins
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kangho Kim
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Elizabeth A. Jacobsen
- Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Cynthia Ju
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
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Shah M, Knights AJ, Vohralik EJ, Psaila AM, Quinlan KGR. Blood and adipose-resident eosinophils are defined by distinct transcriptional profiles. J Leukoc Biol 2023; 113:191-202. [PMID: 36822180 DOI: 10.1093/jleuko/qiac009] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Indexed: 01/21/2023] Open
Abstract
Eosinophils are granular leukocytes of the innate immune system that play important functions in host defense. Inappropriate activation of eosinophils can occur in pathologies such as asthma and esophagitis. However, eosinophils also reside within adipose tissue, where they play homeostatic roles and are important in the activation of thermogenic beige fat. Here we performed bulk RNA sequencing in mouse adipose tissue-resident eosinophils isolated from both subcutaneous and gonadal depots, for the first time, and compared gene expression to blood eosinophils. We found a predominantly conserved transcriptional landscape in eosinophils between adipose depots that is distinct from blood eosinophils in circulation. Through exploration of differentially expressed transcription factors and transcription factors with binding sites enriched in adipose-resident eosinophil genes, we identified KLF, CEBP, and Fos/Jun family members that may drive functional specialization of eosinophils in adipose tissue. These findings increase our understanding of tissue-specific eosinophil heterogeneity, with implications for targeting eosinophil function to treat metabolic disorders such as obesity.
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Affiliation(s)
- Manan Shah
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, High Street, Kensington, New South Wales 2052, Australia
| | - Alexander J Knights
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, High Street, Kensington, New South Wales 2052, Australia
| | - Emily J Vohralik
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, High Street, Kensington, New South Wales 2052, Australia
| | - Annalise M Psaila
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, High Street, Kensington, New South Wales 2052, Australia
| | - Kate G R Quinlan
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, High Street, Kensington, New South Wales 2052, Australia
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Rutkoski CF, Grott SC, Israel NG, Carneiro FE, de Campos Guerreiro F, Santos S, Horn PA, Trentini AA, Barbosa da Silva E, Coelho de Albuquerque CA, Alves TC, Alves de Almeida E. Hepatic and blood alterations in Lithobates catesbeianus tadpoles exposed to sulfamethoxazole and oxytetracycline. CHEMOSPHERE 2022; 307:136215. [PMID: 36041517 DOI: 10.1016/j.chemosphere.2022.136215] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/10/2022] [Accepted: 08/23/2022] [Indexed: 06/15/2023]
Abstract
In this study the effects of environmentally realistic concentrations of the antibiotics sulfamethoxazole (SMX) and oxytetracyclyne (OTC) on Lithobates catesbeianus tadpoles were evaluated, through the analyzes of the frequencies of micronucleus and nuclear abnormalities in erythrocytes, alterations in leucocytes, liver histopathology, and changes in hepatic esterase activities and oxidative stress biomarkers. The animals were exposed for 16 days at concentrations of 0 (control), 20, 90 and 460 ng L-1. No significant difference was found in the frequencies of micronucleus and nuclear abnormalities. The two highest concentrations of SMX and all concentrations of OTC caused a significant increase in the number of lymphocytes. A significant decrease in the number of neutrophils compared to the control group was observed for all concentrations tested of both antibiotics. Also, decrease in the activity of glutathione S-transferase and high histopathological severity scores, indicating liver damage, were found in tadpoles exposed to the two highest concentrations of SMX and all concentrations of OTC. The main changes in the liver histopathology were the presence of inflammatory infiltrate, melanomacrophages, vascular congestion, blood cells and eosinophils. Esterase activities were unchanged. Indeed, the two highest concentrations of OTC caused a reduction in the activities of superoxide dismutase and glucose 6-phosphate dehydrogenase, while the highest concentration inhibited the activity of glutathione peroxidase and increased protein carbonyl levels. These results evidences that environmentally realistic concentrations of SMX and OTC in aquatic environments are capable to significantly disrupt tadpoles' physiology, possibly affecting negatively their survival rate in natural environments.
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Affiliation(s)
- Camila Fatima Rutkoski
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | - Suelen Cristina Grott
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | - Nicole Grasmuk Israel
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | | | | | - Sabrina Santos
- Department of Natural Science, University of Blumenau, Blumenau, SC, Brazil
| | - Priscila Aparecida Horn
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | - Amanda Alves Trentini
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | | | | | - Thiago Caique Alves
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil
| | - Eduardo Alves de Almeida
- Environmental Engineering Post-Graduation Program, University of Blumenau, Blumenau, SC, Brazil; Department of Natural Science, University of Blumenau, Blumenau, SC, Brazil.
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Veletzky L, Eberhardt KA, Hergeth J, Stelzl DR, Zoleko Manego R, Mombo-Ngoma G, Kreuzmair R, Burger G, Adegnika AA, Agnandji ST, Matsiegui PB, Boussinesq M, Mordmüller B, Ramharter M. Distinct loiasis infection states and associated clinical and hematological manifestations in patients from Gabon. PLoS Negl Trop Dis 2022; 16:e0010793. [PMID: 36121900 PMCID: PMC9521832 DOI: 10.1371/journal.pntd.0010793] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 09/29/2022] [Accepted: 09/06/2022] [Indexed: 11/25/2022] Open
Abstract
Background Loiasis–a filarial disease endemic in Central and West Africa–is increasingly recognized as significant individual and public health concern. While the understanding of the disease characteristics remains limited, significant morbidity and excess mortality have been demonstrated. Here, we characterize clinical and hematological findings in a large cohort from Gabon. Methods Loiasis-related clinical manifestations and microfilaremia, hemoglobin and differential blood counts were recorded prospectively during a cross-sectional survey. For analysis, participants were categorized into distinct infection states by the diagnostic criteria of eye worm history and microfilaremia. Results Analysis of data from 1,232 individuals showed that occurrence of clinical and hematological findings differed significantly between the infection states. Eye worm positivity was associated with a wide range of clinical manifestations while microfilaremia by itself was not. Loa loa infection was associated with presence of eosinophilia and absolute eosinophil counts were associated with extent of microfilaremia (p-adj. = 0.012, ß-estimate:0.17[0.04–0.31]). Conclusions Loiasis is a complex disease, causing different disease manifestations in patients from endemic regions. The consequences for the affected individuals or populations as well as the pathophysiological consequences of correlating eosinophilia are largely unknown. High-quality research on loiasis should be fostered to improve patient care and understanding of the disease. Loiasis is a parasitic disease, endemic in parts of Western and Central Africa. While the disease has traditionally been considered to be benign, only recently significant disease morbidity and mortality have been shown. Most of the knowledge about loiasis, however, stems from reports on returning travelers, while comprehensive data from patients living in endemic areas are missing. Blood microfilaremia and reported eye worm are important diagnostic manifestations of the disease, but they can occur independent of each other in affected individuals. We analyzed hematological and clinical findings according to loiasis infection states, comprising reported eye worm and microfilaremia positivity, in a large group of individuals from a highly endemic area. While we found that all loiasis infection states were significantly associated with absolute blood eosinophilia, the eosinophilia was more pronounced in microfilaremic loiasis. Further, there was an association between the extent of microfilaremia and absolute eosinophilia. Analyzing the frequency of clinical disease manifestations, we found that eye worm positive loiasis was associated with a range of symptoms, but microfilaremic loiasis was not. Summarizing, even in highly endemic populations different loiasis infection states are associated with distinct disease manifestations, underlining that loiasis is a versatile and indeed relevant disease.
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Affiliation(s)
- Luzia Veletzky
- Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- German Center For Infection Research (DZIF), Hamburg-Borstel-Riems, Germany
- * E-mail: (LV); (MR)
| | - Kirsten Alexandra Eberhardt
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Daniel Robert Stelzl
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rella Zoleko Manego
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Ghyslain Mombo-Ngoma
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Ruth Kreuzmair
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
| | - Gerrit Burger
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Ayôla Akim Adegnika
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Selidji Todagbe Agnandji
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | | | - Michel Boussinesq
- Institut de Recherche pour le Développement (IRD), UMI 233-TransVIHMI-Inserm U1175-University of Montpellier, Montpellier, France
| | - Benjamin Mordmüller
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany & German Center for Infection Research, partner site Tübingen, Tübingen, Germany
- Radboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
| | - Michael Ramharter
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep. of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
- German Center For Infection Research (DZIF), Hamburg-Borstel-Riems, Germany
- * E-mail: (LV); (MR)
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Xu L, Yang Y, Wen Y, Jeong JM, Emontzpohl C, Atkins CL, Sun Z, Poulsen KL, Hall DR, Steve Bynon J, Gao B, Lee WM, Rule J, Jacobsen EA, Wang H, Ju C. Hepatic recruitment of eosinophils and their protective function during acute liver injury. J Hepatol 2022; 77:344-352. [PMID: 35259470 PMCID: PMC9308653 DOI: 10.1016/j.jhep.2022.02.024] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear. METHODS Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33-/- mice and macrophage-depleted mice, as well as in vitro cultures of eosinophils and macrophages, were performed to interrogate the mechanism of eotaxin-2 (CCL24) production. RESULTS Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver failure, whereas few eosinophils were detectable in healthy liver tissues. In mice treated with APAP, carbon tetrachloride or concanavalin A, eosinophils were recruited into the liver and played a profound protective role. Mice deficient of macrophages or IL-33 exhibited impaired hepatic eosinophil recruitment during acute liver injury. CCL24, but not CCL11, was increased after treatment of each hepatotoxin in an IL-33 and macrophage-dependent manner. In vitro experiments demonstrated that IL-33, by stimulating IL-4 release from eosinophils, promoted the production of CCL24 by macrophages. CONCLUSIONS This is the first study to demonstrate that hepatic recruitment of and protection by eosinophils occur commonly in various models of acute liver injury. Our findings support further exploration of eosinophils as a therapeutic target to treat APAP-induced acute liver injury. LAY SUMMARY The current study unveils that eosinophils are recruited into the liver and play a protective function during acute liver injury caused by acetaminophen overdose. The data demonstrate that IL-33-activated eosinophils trigger macrophages to release high amounts of CCL24, which promotes hepatic eosinophil recruitment. Our findings suggest that eosinophils could be an effective cell-based therapy for the treatment of acetaminophen-induced acute liver injury.
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Affiliation(s)
- Long Xu
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, China
| | - Yang Yang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Yankai Wen
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jong-Min Jeong
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Christoph Emontzpohl
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Constance L Atkins
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Zhaoli Sun
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kyle L Poulsen
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - David R Hall
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - J Steve Bynon
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Bin Gao
- Laboratory of Liver Disease, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
| | - Jody Rule
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
| | - Elizabeth A Jacobsen
- Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
| | - Cynthia Ju
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
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Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection. Cell Rep 2022; 40:111144. [PMID: 35905725 PMCID: PMC9460869 DOI: 10.1016/j.celrep.2022.111144] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/19/2022] [Accepted: 07/06/2022] [Indexed: 12/15/2022] Open
Abstract
Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice, in which they support host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb exposure. In mice this influx is CCR3 independent and instead requires cell-intrinsic expression of the oxysterol receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interact directly with bacilli-laden alveolar macrophages, which upregulate the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment is impaired in Ch25h-deficient mice. Our findings show that eosinophils are among the earliest cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a role for GPR183 in the migration of eosinophils into lung tissue. Eosinophils are usually associated with allergy or type II responses. Here, Bohrer et al. show that eosinophils are rapidly recruited to the lungs after respiratory infection with the intracellular pathogen Mycobacterium tuberculosis through the oxysterol sensor GPR183.
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Tao Z, Zhu H, Zhang J, Huang Z, Xiang Z, Hong T. Recent advances of eosinophils and its correlated diseases. Front Public Health 2022; 10:954721. [PMID: 35958837 PMCID: PMC9357997 DOI: 10.3389/fpubh.2022.954721] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/04/2022] [Indexed: 11/22/2022] Open
Abstract
Eosinophils are differentiated by bone marrow multipotent progenitor cells and are further released into peripheral blood after maturation. Human eosinophils can exhibit unique multi-leaf nuclear morphology, which are filled with cytoplasmic granules that contain cytotoxicity and immune regulatory proteins. In recent years, many studies focused on the origin, differentiation and development process of eosinophils. It has been discovered that the eosinophils have the regulatory functions of innate and adaptive immunity, and can also function in several diseases, including asthma, chronic obstructive pulmonary diseases, acute respiratory distress syndrome, malignant tumors and so on. Hence, the role and effects of eosinophils in various diseases are emphasized. In this review, we comprehensively summarized the development and differentiation process of eosinophils, the research progress of their related cytokines, diseases and current clinical treatment options, and discussed the potential drug target, aiming to provide a theoretical and practical basis for the clinical prevention and treatment of eosinophil-related diseases, especially respiratory diseases. To conclude, the guiding significance of future disease treatment is proposed based on the recent updated understandings into the cell functions of eosinophils.
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Affiliation(s)
- Zhang Tao
- Department of Pulmonary Diseases, Yancheng Traditional Chinese Medicine Hospital, Yancheng, China
| | - Hua Zhu
- Department of Gastroenterology, Yancheng Third People's Hospital, Yancheng, China
- School of Medicine, Affiliated Yancheng Hospital, Southeast University, Yancheng, China
| | - Jiateng Zhang
- Zhejiang University School of Medicine, Hangzhou, China
- Chu Kochen Honors College of Zhejiang University, Hangzhou, China
| | - Zhiming Huang
- Zhejiang University School of Medicine, Hangzhou, China
- Chu Kochen Honors College of Zhejiang University, Hangzhou, China
| | - Ze Xiang
- Zhejiang University School of Medicine, Hangzhou, China
- Chu Kochen Honors College of Zhejiang University, Hangzhou, China
| | - Tu Hong
- Zhejiang University School of Medicine, Hangzhou, China
- Chu Kochen Honors College of Zhejiang University, Hangzhou, China
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40
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Whyte CE, Singh K, Burton OT, Aloulou M, Kouser L, Veiga RV, Dashwood A, Okkenhaug H, Benadda S, Moudra A, Bricard O, Lienart S, Bielefeld P, Roca CP, Naranjo-Galindo FJ, Lombard-Vadnais F, Junius S, Bending D, Ono M, Hochepied T, Halim TY, Schlenner S, Lesage S, Dooley J, Liston A. Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits. J Exp Med 2022; 219:e20212391. [PMID: 35699942 PMCID: PMC9202720 DOI: 10.1084/jem.20212391] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 04/06/2022] [Accepted: 05/16/2022] [Indexed: 12/17/2022] Open
Abstract
Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.
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Affiliation(s)
- Carly E. Whyte
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | - Kailash Singh
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | - Oliver T. Burton
- Immunology Programme, The Babraham Institute, Cambridge, UK
- VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven—University of Leuven, Leuven, Belgium
| | - Meryem Aloulou
- Immunology Programme, The Babraham Institute, Cambridge, UK
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Centre national de la recherche scientifique U5051, Institut national de la santé et de la recherche médicale U1291, University of Toulouse III, Toulouse, France
| | - Lubna Kouser
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | | | - Amy Dashwood
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | | | - Samira Benadda
- Immunology Programme, The Babraham Institute, Cambridge, UK
- Centre de Recherche Sur L’inflammation, Centre national de la recherche scientifique ERL8252, Institut national de la santé et de la recherche médicale U1149, Université de Paris, Paris, France
| | - Alena Moudra
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | - Orian Bricard
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | | | | | - Carlos P. Roca
- Immunology Programme, The Babraham Institute, Cambridge, UK
| | | | - Félix Lombard-Vadnais
- Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada
- Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Quebec, Canada
| | - Steffie Junius
- VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven—University of Leuven, Leuven, Belgium
| | - David Bending
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Masahiro Ono
- Department of Life Sciences, Imperial College London, London, UK
| | - Tino Hochepied
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- VIB Center for Inflammation Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium
| | | | - Susan Schlenner
- Department of Microbiology, Immunology and Transplantation, KU Leuven—University of Leuven, Leuven, Belgium
| | - Sylvie Lesage
- Centre de Recherche Sur L’inflammation, Centre national de la recherche scientifique ERL8252, Institut national de la santé et de la recherche médicale U1149, Université de Paris, Paris, France
- Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Quebec, Canada
| | - James Dooley
- Immunology Programme, The Babraham Institute, Cambridge, UK
- VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven—University of Leuven, Leuven, Belgium
| | - Adrian Liston
- Immunology Programme, The Babraham Institute, Cambridge, UK
- VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven—University of Leuven, Leuven, Belgium
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Solomon Y, Woldu B, Mesfin N, Enawgaw B. Selected hematological abnormalities and their associated factors among asthmatic patients in Northwest Ethiopia: a cross-sectional study. BMC Pulm Med 2022; 22:228. [PMID: 35698065 PMCID: PMC9190135 DOI: 10.1186/s12890-022-02020-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/03/2022] [Indexed: 11/17/2022] Open
Abstract
Background Asthma is a chronic inflammatory disease that affects the lungs. Variation in whole blood cell lines is caused by the progression and severity of asthma. Common hematological abnormalities encountered during asthma include eosinophilia, neutrophilia, leukocytosis, and increased erythrocyte sedimentation rate. The main aim of this study was to assess the selected hematological abnormalities and their associated factors among asthmatic patients in Northwest Ethiopia from March to May 2021. Methodology A hospital-based cross-sectional study was conducted on a total of 320 asthmatic patients in Northwest Ethiopia. A simple random sampling technique was employed to select study participants. A pre-tested structured questionnaire and a checklist were used to collect data. Blood samples were collected from asthmatic patients for complete blood count and erythrocyte sedimentation rate determination. Hematological profiles were analyzed by Unicel DxH 800 (Beckman Coulter, Ireland). The erythrocyte sedimentation rate was determined by using the Westergren method. The data were entered into EpiData version 3.0.4 and analyzed with a statistical package for social science version 20 software. The bi-variable and multi-variable binary logistic regression models were used to assess the factors associated with hematological abnormalities. A p value of less than 0.05 in the multivariable logistic regression analysis was considered statistically significant. Results The overall prevalence of neutrophilia, eosinophilia, thrombocytopenia, leukocytosis, and basophilia was 35.3%, 20%, 11.9%, 10.3%, and 4.1%, respectively. Neutrophilia was associated with a lack of physical activity (AOR = 3.25; 95% CI 1.43–7.37) and a history of taking non-asthmatic drugs within the previous three months (AOR = 2.63; 95% CI 1.22–5.65). Being admitted to the emergency department (AOR = 0.27; 95% CI 0.11–5.67) was found to be associated with eosinophilia. In addition, being admitted to the emergency department (AOR = 5.44; 95%CI: 2.6–11.3) was associated with thrombocytopenia. Conclusion The current study demonstrated the predominant prevalence of neutrophilia, followed by eosinophilia, among asthma patients. Therefore, hematological abnormalities should be taken into account for proper monitoring and management of asthmatic patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02020-z.
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Affiliation(s)
- Yenealem Solomon
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia.
| | - Berhanu Woldu
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
| | - Nebiyu Mesfin
- Department of Internal Medicine, School of Medicine, University of Gondar, Gondar, Ethiopia
| | - Bamlaku Enawgaw
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
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Sakyi SA, Amoani B, Opoku S, Dzata L, Aniagyei W, Senu E, Dankwa K, Wilson MD. Assessing the role of eosinophil-mediated immune response markers in detecting hookworm infection: A case-control study in Kintampo, Ghana. Health Sci Rep 2022; 5:e674. [PMID: 35662977 PMCID: PMC9165202 DOI: 10.1002/hsr2.674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/22/2022] [Accepted: 05/23/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Aim Human hookworm disease caused by Ancylostoma duodenale and Necator americanus is a serious public health problem. Hookworm infection activates eosinophil‐mediated tissue inflammatory responses, involving the production of the eosinophil‐specific chemokine (eotaxin), recruitment of eosinophils, secretion of the cationic protein, and production of antiparasite immunoglobulin E (IgE). We investigated eosinophil‐mediated immune response as markers (CCL11, eosinophil cationic protein [ECP], and IgE) for detecting hookworm infection. Methods This case‐control study was carried out in hookworm endemic areas within the Kintampo North Municipality.Forty hookworm‐positive subjects and 36 apparently healthy individuals were recruited as cases and controls, respectively. Stool samples were collected for hookworm detection by the Kato–Katz technique and speciation by polymerase chain reaction. Approximately, 5 ml of intravenous blood was used to obtain plasma for the immunological assays. Results Of eosinophil‐mediated immune response markers studied, ECP and CCL11 were significantly higher among hookworm patients compared to controls. Increasing CCL11 (β = −0.81, p = 0.015) was associated with a significant decrease hookworm intensity. However, increasing eosinophil count (β = 0.62, p = 0.027) was associated with significant increase in hookworm intensity. In receiver operator characteristics analysis, ECP could significantly detect hookworm infection with a very high area under the curve (AUC) (AUC = 0.97, p < 0.0001). At a cutoff of 39.05, ECP was the best eosinophil‐mediated immune response marker for detecting hookworm infection with a sensitivity of 97.2%, specificity of 87.8%, a positive predictive value of 89.7%, and a negative predictive value of 96.6%. Conclusion ECP best predicts eosinophil‐mediated immune response for detecting hookworm infection, while CCL11 and eosinophil count better predict the intensity of hookworm. Moreover, the ECP level is a good indicator of hookworm infection and intensity and may require additional investigations to augment current hookworm diagnostic techniques.
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Affiliation(s)
- Samuel A Sakyi
- Department of Molecular Medicine, School of Medicine and Dentistry Kwame Nkrumah University of Science and Technology Kumasi Ghana
| | - Benjamin Amoani
- Department of Biomedical Science, School of Medicine and Dentistry University of Cape Coast Cape Coast Ghana
| | - Stephen Opoku
- Department of Molecular Medicine, School of Medicine and Dentistry Kwame Nkrumah University of Science and Technology Kumasi Ghana
| | - Lawrence Dzata
- Department of Microbiology and Immunology, School of Medical Sciences University of Cape Coast Cape Coast Ghana
| | - Wilfred Aniagyei
- Department of Biomedical Science, School of Medicine and Dentistry University of Cape Coast Cape Coast Ghana
| | - Ebenezer Senu
- Department of Molecular Medicine, School of Medicine and Dentistry Kwame Nkrumah University of Science and Technology Kumasi Ghana
| | - Kwabena Dankwa
- Department of Microbiology and Immunology, School of Medical Sciences University of Cape Coast Cape Coast Ghana
| | - Michael D Wilson
- Parasitology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences University of Ghana Legon Ghana
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Radonjic-Hoesli S, Martignoni Z, Cazzaniga S, Furrer DI, Simon HU, Bürgler C, Simon D. Characteristics of Dermatological Patients With Blood Eosinophilia: A Retrospective Analysis of 453 Patients. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:1229-1237.e8. [PMID: 35247633 DOI: 10.1016/j.jaip.2022.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 01/10/2022] [Accepted: 02/04/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Skin diseases associated with blood or tissue eosinophilia are common. Because these have various clinical manifestations, making the correct diagnosis can be challenging. So far, dermatological patients with concomitant blood eosinophilia have not been characterized. OBJECTIVE To investigate patterns of dermatological patients with concomitant blood eosinophilia to obtain information helpful for optimizing disease management. METHODS In this retrospective study, demographic and clinical data and diagnostic test results of all patients presenting with dermatoses associated with blood eosinophilia referred to a university center from 2014 to 2018 were extracted from the electronic patient charts and evaluated using descriptive and semantic map analyses. RESULTS A total of 453 patients (51.4% females; mean age, 58.4 ± 21.7 years) were included and grouped according to blood absolute eosinophil counts: severe, greater than or equal to 1.5 G/L (n = 87; 19.2%); moderate, 1.0 to 1.49 G/L (n = 73; 16.1%); and mild eosinophilia, 0.5 to 0.99 G/L (n = 293; 64.7%). Most patients presented with chronic (64.6%), generalized skin lesions (75.9%), and pruritus (88.1%). Statistical analyses revealed 3 distinct patterns: (1) mild eosinophilia associated with localized skin disease, age less than 50 years, history of atopy, and diagnosis of eczema or infectious disease; (2) moderate eosinophilia linked to generalized skin lesions, pruritus, age more than 70 years, and autoimmune bullous disease; and (3) severe eosinophilia associated with diagnosis of hypereosinophilic syndromes, drug hypersensitivity, or malignant disease. CONCLUSIONS Based on the pattern analysis of patients with dermatoses associated with blood eosinophilia, a diagnostic workup has been developed aiming at setting the correct differential diagnosis in a feasible and effective manner.
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Affiliation(s)
- Susanne Radonjic-Hoesli
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Zora Martignoni
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Simone Cazzaniga
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Centro Studi GISED, Bergamo, Italy
| | - Dominique Isabel Furrer
- Insel Data Science Center, Directorate of Teaching and Research, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland; Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia; Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia; Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
| | - Christina Bürgler
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
| | - Dagmar Simon
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Arnhold J, Malle E. Halogenation Activity of Mammalian Heme Peroxidases. Antioxidants (Basel) 2022; 11:antiox11050890. [PMID: 35624754 PMCID: PMC9138014 DOI: 10.3390/antiox11050890] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 12/10/2022] Open
Abstract
Mammalian heme peroxidases are fascinating due to their unique peculiarity of oxidizing (pseudo)halides under physiologically relevant conditions. These proteins are able either to incorporate oxidized halides into substrates adjacent to the active site or to generate different oxidized (pseudo)halogenated species, which can take part in multiple (pseudo)halogenation and oxidation reactions with cell and tissue constituents. The present article reviews basic biochemical and redox mechanisms of (pseudo)halogenation activity as well as the physiological role of heme peroxidases. Thyroid peroxidase and peroxidasin are key enzymes for thyroid hormone synthesis and the formation of functional cross-links in collagen IV during basement membrane formation. Special attention is directed to the properties, enzymatic mechanisms, and resulting (pseudo)halogenated products of the immunologically relevant proteins such as myeloperoxidase, eosinophil peroxidase, and lactoperoxidase. The potential role of the (pseudo)halogenated products (hypochlorous acid, hypobromous acid, hypothiocyanite, and cyanate) of these three heme peroxidases is further discussed.
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Affiliation(s)
- Jürgen Arnhold
- Medical Faculty, Institute of Medical Physics and Biophysics, Leipzig University, 04107 Leipzig, Germany
- Correspondence: (J.A.); or (E.M.)
| | - Ernst Malle
- Gottfried Schatz Research Center, Division of Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
- Correspondence: (J.A.); or (E.M.)
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Chen SY, Qiu QG, Mo HL, Gong TF, Li F, He JL, Li WC, Xie XR, Liu W. Molecular Identification and Phylogenetic Analysis of Ascarids in Wild Animals. Front Vet Sci 2022; 9:891672. [PMID: 35573413 PMCID: PMC9100682 DOI: 10.3389/fvets.2022.891672] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Ascarid nematodes are the most common and harmful nematodes parasites in animals. By analyzing genetic variation, this study explores the genetic and phylogenetic relationship among ascarids from 11 different hosts. This study collected ascarid samples from the feces of nine animal species in Changsha Ecological Zoo of Hunan Province and two animal kinds in the College of Veterinary Medicine of Hunan Agricultural University. The mitochondrial gene (pcox1) and ribosomal ITS sequences were amplified, sequenced, and analyzed by PCR to identify the species of the samples. The phylogenetic tree was constructed based on two genes (cox1 and ITS) by the Neighbor-joining method, and the phylogenetic relationship was analyzed. The sequencing results showed that the sequence lengths of pcox1 and ITS genes in the samples were 441 bp and 838–1,177 bp, respectively. The difference rates were 0.00–1.70% in pcox1 gene and 0.00–7.30% in ITS gene. Phylogenetic analysis showed that ascarid worms from the white lion, Northeast tiger, South China tiger and cheetah were identified as Toxascaris leonina. Ascarids from the zebra were identified as Parascaris equorum, while those from chicken and peacocks were identified as Ascaridia galli. Ascarids of wolf and dog origin were Toxocara canis, the snake ascarids belonged to Ophidascaris filaria, and the bear ascarids belonged to Baylisascaris transfuga. There was a significant gap between different kinds of ascarid worms. We found that these two mitochondrial genes pcox1 and ITS showed a common characteristic that the intraspecific differences were significantly smaller than the interspecific differences, confirming that these two genes could be used as interspecific genetic markers for molecular identification of different ascarids origins. The intraspecific variation rate of the ITS gene was higher than that of pcox1, indicating that ITS can also be used in the genetic research of Ascaris species development. This study revealed the genetic evolution and phylogeny of ascarids in wild animals, and our results will help prevent and control ascarids in wild animals.
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Affiliation(s)
- Shu-Yu Chen
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
- The Key Laboratory of Animal Vaccine & Protein Engineering, Changsha, China
| | | | - Hai-Long Mo
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Teng-Fang Gong
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Fen Li
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Jun-Lin He
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Wen-Chao Li
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Xin-Rui Xie
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
| | - Wei Liu
- Research Center for Parasites & Vectors, College of Veterinary Medicine, Hunan Agricultural University, Changsha, China
- The Key Laboratory of Animal Vaccine & Protein Engineering, Changsha, China
- *Correspondence: Wei Liu
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Recombinant dynein light intermediate chain of Haemonchus contortus affects the functions of goat immune cells in vitro. Parasitol Res 2022; 121:1699-1707. [DOI: 10.1007/s00436-022-07510-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/27/2022] [Indexed: 10/18/2022]
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Relevance of Helminth-Microbiota Interplay in the Host Immune Response. Cell Immunol 2022; 374:104499. [DOI: 10.1016/j.cellimm.2022.104499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 02/27/2022] [Accepted: 03/01/2022] [Indexed: 11/16/2022]
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Vielmo A, Schwertz CI, Piva MM, Echenique JVZ, De Lorenzo C, Surita LE, de Andrade CP, Sonne L. Eosinophilic meningoencephalitis caused by rat lungworm (Angiostrongylus cantonensis) migration in a white-eared opossum (Didelphis albiventris) with concurrent distemper virus in southern Brazil. Parasitol Res 2022; 121:1545-1549. [PMID: 35192069 DOI: 10.1007/s00436-022-07471-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/14/2022] [Indexed: 11/26/2022]
Abstract
Angiostrongylus cantonensis is a worldwide zoonotic parasite that causes eosinophilic meningoencephalitis in many species of animals including humans. This report describes neuro-angiostrongylosis in a white-eared opossum that showed nervous clinical signs such as circling and depression. At necropsy, no relevant macroscopic lesions were observed. Histologically, eosinophilic meningoencephalitis was associated with multiple sections of nematodes and many intracytoplasmic eosinophilic inclusion bodies within gastric parietal cells. Immunohistochemistry was strongly positive for canine distemper virus in the stomach but there was no immunolabeling in the brain. This study describes a fatal case of eosinophilic meningoencephalitis by A. cantonensis with canine distemper virus concurrent infection in a white-eared opossum in southern Brazil, with histological characterization and molecular confirmation of the parasitism.
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Affiliation(s)
- Andréia Vielmo
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil.
| | - Claiton Ismael Schwertz
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
| | - Manoela Marchezan Piva
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
| | - Joanna Vargas Zillig Echenique
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
| | - Cíntia De Lorenzo
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
| | - Lívia Eichenberg Surita
- PRESERVAS-Núcleo de Conservação e Reabilitação de Animais Silvestres, Hospital de Clínicas Veterinárias, Universidade Federal Do Rio Grande Do Sul (UFRGS), Avenida Bento Gonçalves 9090, Agronomia, Porto Alegre, RS, 91540-000, Brazil
| | - Caroline Pinto de Andrade
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
| | - Luciana Sonne
- Departamento de Patologia Clínica Veterinária, Setor de Patologia Veterinária, Faculdade de Veterinária, Universidade Federal Do Rio Grande Do Sul (UFRGS), Av. Bento Gonçalves 9090, Prédio 42505, Porto Alegre, RS, 91540-000, Brazil
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Abstract
Intestinal nematode infections caused by soil-transmitted helminths (STH), such as the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura, and the hookworms Ancylostoma duodenale, and Necator americanus, infect more than 1 billion people throughout the world. School-aged children tend to harbor the greatest numbers of intestinal worms, and as a result, experience more adverse health consequences, such as poor growth, anemia, and cognitive decline. Clinicians should maintain a high degree of suspicion in endemic areas when patients present with surgical abdomens, particularly children. Current antihelminthic drugs are moderately effective, but reinfection is possible. Global efforts are needed to eradicate STH infections.
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Affiliation(s)
- Angela F Veesenmeyer
- Department of Child Health, University of Arizona College of Medicine-Phoenix, Pediatric Infectious Disease, Valleywise Health Medical Center, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA.
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Macháček T, Leontovyč R, Šmídová B, Majer M, Vondráček O, Vojtěchová I, Petrásek T, Horák P. Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice. PLoS Pathog 2022; 18:e1010302. [PMID: 35120185 PMCID: PMC8849443 DOI: 10.1371/journal.ppat.1010302] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 02/16/2022] [Accepted: 01/24/2022] [Indexed: 12/17/2022] Open
Abstract
Helminth neuroinfections represent serious medical conditions, but the diversity of the host-parasite interplay within the nervous tissue often remains poorly understood, partially due to the lack of laboratory models. Here, we investigated the neuroinvasion of the mouse spinal cord by Trichobilharzia regenti (Schistosomatidae). Active migration of T. regenti schistosomula through the mouse spinal cord induced motor deficits in hindlimbs but did not affect the general locomotion or working memory. Histological examination of the infected spinal cord revealed eosinophilic meningomyelitis with eosinophil-rich infiltrates entrapping the schistosomula. Flow cytometry and transcriptomic analysis of the spinal cord confirmed massive activation of the host immune response. Of note, we recorded striking upregulation of the major histocompatibility complex II pathway and M2-associated markers, such as arginase or chitinase-like 3. Arginase also dominated the proteins found in the microdissected tissue from the close vicinity of the migrating schistosomula, which unselectively fed on the host nervous tissue. Next, we evaluated the pathological sequelae of T. regenti neuroinvasion. While no demyelination or blood-brain barrier alterations were noticed, our transcriptomic data revealed a remarkable disruption of neurophysiological functions not yet recorded in helminth neuroinfections. We also detected DNA fragmentation at the host-schistosomulum interface, but schistosomula antigens did not affect the viability of neurons and glial cells in vitro. Collectively, altered locomotion, significant disruption of neurophysiological functions, and strong M2 polarization were the most prominent features of T. regenti neuroinvasion, making it a promising candidate for further neuroinfection research. Indeed, understanding the diversity of pathogen-related neuroinflammatory processes is a prerequisite for developing better protective measures, treatment strategies, and diagnostic tools.
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Affiliation(s)
- Tomáš Macháček
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
| | - Roman Leontovyč
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
| | - Barbora Šmídová
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
| | - Martin Majer
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
| | - Oldřich Vondráček
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
| | - Iveta Vojtěchová
- National Institute of Mental Health, Klecany, Czechia
- Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia
| | - Tomáš Petrásek
- National Institute of Mental Health, Klecany, Czechia
- Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia
| | - Petr Horák
- Department of Parasitology, Faculty of Science, Charles University, Prague, Czechia
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