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Lee MJ, Shin S, Kim HW, Ko MK, Park SH, Kim SM, Park JH. Oral Administration of Zinc Sulfate with Intramuscular Foot-and-Mouth Disease Vaccine Enhances Mucosal and Systemic Immunity. Vaccines (Basel) 2024; 12:1268. [PMID: 39591171 PMCID: PMC11598382 DOI: 10.3390/vaccines12111268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/01/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Foot-and-mouth disease (FMD) remains a significant global threat to livestock farming. Current commercial FMD vaccines present several challenges, including the risk of infection and adverse injection site reactions due to oil-based adjuvants. The complex immune environment of the gut-associated lymphoid tissue has the potential to induce broad and diverse immune responses. Therefore, we aimed to explore the potential of zinc sulfate as an oral adjuvant to enhance intestinal mucosal immunity and complement the effects of intramuscular (IM) FMD vaccination. Methods: We conducted serological analyses on mice and pigs, measuring secretory IgA (sIgA) levels and evaluating the expression of mucosal immunity-related genes in pigs. These assessments were used to investigate the systemic and mucosal immune responses induced by oral zinc sulfate administration in combination with an IM FMD vaccine. Results: This combination strategy significantly increased structural protein antibody titers and virus neutralization titers in experimental animals (mice) and target animals (pigs) across early, mid-, and long-term periods. Additionally, this approach enhanced the expression of key cytokines associated with mucosal immunity and increased sIgA levels, which are critical markers of mucosal immunity. Conclusions: Oral zinc sulfate administration may synergize with inactivated FMD vaccines, leading to sustained and enhanced long-term immune responses. This novel strategy could reduce the frequency of required vaccinations or allow for a lower antigen dose in vaccines, effectively stimulating the mucosal immune system and boosting systemic immunity. This approach has the potential to improve the overall efficacy of commercial FMD vaccines.
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Carreto-Binaghi LE, Sztein MB, Booth JS. Role of cellular effectors in the induction and maintenance of IgA responses leading to protective immunity against enteric bacterial pathogens. Front Immunol 2024; 15:1446072. [PMID: 39324143 PMCID: PMC11422102 DOI: 10.3389/fimmu.2024.1446072] [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: 06/08/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
The mucosal immune system is a critical first line of defense to infectious diseases, as many pathogens enter the body through mucosal surfaces, disrupting the balanced interactions between mucosal cells, secretory molecules, and microbiota in this challenging microenvironment. The mucosal immune system comprises of a complex and integrated network that includes the gut-associated lymphoid tissues (GALT). One of its primary responses to microbes is the secretion of IgA, whose role in the mucosa is vital for preventing pathogen colonization, invasion and spread. The mechanisms involved in these key responses include neutralization of pathogens, immune exclusion, immune modulation, and cross-protection. The generation and maintenance of high affinity IgA responses require a delicate balance of multiple components, including B and T cell interactions, innate cells, the cytokine milieu (e.g., IL-21, IL-10, TGF-β), and other factors essential for intestinal homeostasis, including the gut microbiota. In this review, we will discuss the main cellular components (e.g., T cells, innate lymphoid cells, dendritic cells) in the gut microenvironment as mediators of important effector responses and as critical players in supporting B cells in eliciting and maintaining IgA production, particularly in the context of enteric infections and vaccination in humans. Understanding the mechanisms of humoral and cellular components in protection could guide and accelerate the development of more effective mucosal vaccines and therapeutic interventions to efficiently combat mucosal infections.
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Affiliation(s)
- Laura E. Carreto-Binaghi
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States
- Laboratorio de Inmunobiologia de la Tuberculosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
| | - Marcelo B. Sztein
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
- Tumor Immunology and Immunotherapy Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States
| | - Jayaum S. Booth
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States
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3
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Gleeson PJ, Monteiro RC. The Role of Mucosal Immunity: What Can We Learn From Animal and Human Studies? Semin Nephrol 2024; 44:151566. [PMID: 40082160 DOI: 10.1016/j.semnephrol.2025.151566] [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] [Indexed: 03/16/2025]
Abstract
Immunoglobulin A (IgA) is a key actor in the mucosal immune system, which moderates interactions between the host and environmental factors such as food antigens and commensal microorganisms. The pathogenesis of IgA nephropathy (IgAN) involves a multistep process starting with deglycosylation of mucosally derived, polymeric IgA1 (dg-IgA1) that reaches the circulation. Modified O-glycans on dg-IgA1 are targeted by IgG-autoantibodies, leading to the formation of circulating immune complexes that deposit in the glomerular mesangium. Infections of mucosal surfaces trigger flares of primary IgAN, while inflammatory bowel disease and liver cirrhosis are important causes of secondary IgAN, supporting a mucosal source of nephritogenic IgA1. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T-cell-dependent or T-cell-independent B-cell differentiation into IgA-secreting plasma cells. Herein we review the literature concerning mucosal immune function and how it is altered in this disease. We discuss recent evidence supporting a causal role of gut microbiota dysbiosis in IgAN pathogenesis.
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Affiliation(s)
- Patrick J Gleeson
- Paris Cité University, Center for Research on Inflammation, Paris, France; Inserm, UMR1149; CNRS EMR8252; Inflamex Laboratory of Excellence; Nephrology Department.
| | - Renato C Monteiro
- Paris Cité University, Center for Research on Inflammation, Paris, France; Inserm, UMR1149; CNRS EMR8252; Inflamex Laboratory of Excellence; Immunology laboratory of Bichat hospital, Paris, France
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4
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Brenchley JM, Serrano-Villar S. From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy. MICROBIOME 2024; 12:113. [PMID: 38907315 PMCID: PMC11193286 DOI: 10.1186/s40168-024-01825-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 04/26/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Although the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV. RESULTS Here, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents. CONCLUSIONS Our review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.
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Affiliation(s)
- Jason M Brenchley
- Barrier Immunity Section, Lab of Viral Diseases, NIAID, NIH, Bethesda, MA, USA.
| | - Sergio Serrano-Villar
- Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, IRYCIS and CIBERInfec, Madrid, Spain.
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5
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Eriksen C, Moll JM, Myers PN, Pinto ARA, Danneskiold-Samsøe NB, Dehli RI, Rosholm LB, Dalgaard MD, Penders J, Jonkers DM, Pan-Hammarström Q, Hammarström L, Kristiansen K, Brix S. IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency. Nat Commun 2023; 14:8124. [PMID: 38065985 PMCID: PMC10709418 DOI: 10.1038/s41467-023-44007-2] [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: 12/22/2021] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
Immunoglobulin A (IgA) is acknowledged to play a role in the defence of the mucosal barrier by coating microorganisms. Surprisingly, IgA-deficient humans exhibit few infection-related complications, raising the question if the more specific IgG may help IgM in compensating for the lack of IgA. Here we employ a cohort of IgA-deficient humans, each paired with IgA-sufficient household members, to investigate multi-Ig bacterial coating. In IgA-deficient humans, IgM alone, and together with IgG, recapitulate coating of most bacterial families, despite an overall 3.6-fold lower Ig-coating. Bacterial IgG coating is dominated by IgG1 and IgG4. Single-IgG2 bacterial coating is sparse and linked to enhanced Escherichia coli load and TNF-α. Although single-IgG2 coating is 1.6-fold more prevalent in IgA deficiency than in healthy controls, it is 2-fold less prevalent than in inflammatory bowel disease. Altogether we demonstrate that IgG assists IgM in coating of most bacterial families in the absence of IgA and identify single-IgG2 bacterial coating as an inflammatory marker.
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Affiliation(s)
- Carsten Eriksen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Janne Marie Moll
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Pernille Neve Myers
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Ana Rosa Almeida Pinto
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | | | - Rasmus Ibsen Dehli
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Lisbeth Buus Rosholm
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | | | - John Penders
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, NUTRIM School for Nutrition and Translational Research in Metabolism & Care and Public Health Research Institute CAPHRI, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Daisy Mae Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Qiang Pan-Hammarström
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Lennart Hammarström
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Karsten Kristiansen
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
- BGI-Shenzhen, Shenzhen, China
- Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, Shandong, China
| | - Susanne Brix
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
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6
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Das S, Stamnaes J, Kemppainen E, Hervonen K, Lundin KEA, Parmar N, Jahnsen FL, Jahnsen J, Lindfors K, Salmi T, Iversen R, Sollid LM. Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2300401. [PMID: 37424036 PMCID: PMC10477854 DOI: 10.1002/advs.202300401] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 06/23/2023] [Indexed: 07/11/2023]
Abstract
Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.
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Affiliation(s)
- Saykat Das
- Department of ImmunologyOslo University Hospital‐RikshospitaletOslo0372Norway
- KG Jebsen Coeliac Disease Research CentreInstitute of Clinical MedicineUniversity of OsloOslo0372Norway
| | - Jorunn Stamnaes
- Department of ImmunologyOslo University Hospital‐RikshospitaletOslo0372Norway
- KG Jebsen Coeliac Disease Research CentreInstitute of Clinical MedicineUniversity of OsloOslo0372Norway
| | - Esko Kemppainen
- Celiac Disease Research CentreFaculty of Medicine and Health TechnologyTampere UniversityTampere33520Finland
| | - Kaisa Hervonen
- Celiac Disease Research CentreFaculty of Medicine and Health TechnologyTampere UniversityTampere33520Finland
- Department of DermatologyTampere University HospitalTampere33520Finland
| | - Knut E. A. Lundin
- KG Jebsen Coeliac Disease Research CentreInstitute of Clinical MedicineUniversity of OsloOslo0372Norway
- Department of GastroenterologyOslo University Hospital‐RikshospitaletOslo0372Norway
| | - Naveen Parmar
- Department of PathologyUniversity of Oslo and Institute of Clinical MedicineOslo University Hospital‐RikshospitaletOslo0372Norway
| | - Frode L. Jahnsen
- Department of PathologyUniversity of Oslo and Institute of Clinical MedicineOslo University Hospital‐RikshospitaletOslo0372Norway
| | - Jørgen Jahnsen
- Department of GastroenterologyAkershus University HospitalLørenskog1478Norway
| | - Katri Lindfors
- Celiac Disease Research CentreFaculty of Medicine and Health TechnologyTampere UniversityTampere33520Finland
| | - Teea Salmi
- Celiac Disease Research CentreFaculty of Medicine and Health TechnologyTampere UniversityTampere33520Finland
| | - Rasmus Iversen
- Department of ImmunologyOslo University Hospital‐RikshospitaletOslo0372Norway
- KG Jebsen Coeliac Disease Research CentreInstitute of Clinical MedicineUniversity of OsloOslo0372Norway
| | - Ludvig M. Sollid
- Department of ImmunologyOslo University Hospital‐RikshospitaletOslo0372Norway
- KG Jebsen Coeliac Disease Research CentreInstitute of Clinical MedicineUniversity of OsloOslo0372Norway
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7
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Tamura H. IgA nephropathy associated with Crohn's disease. World J Methodol 2023; 13:67-78. [PMID: 37456980 PMCID: PMC10348078 DOI: 10.5662/wjm.v13.i3.67] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/16/2023] [Accepted: 05/12/2023] [Indexed: 06/20/2023] Open
Abstract
The relationship between IgA nephropathy (IgAN) and Crohn’s disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.
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Affiliation(s)
- Hiroshi Tamura
- Department of Pediatrics, Kumamoto University, Kumamoto 8608556, Japan
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8
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Novak J, Renfrow MB, King RG, Reily C, Green TJ. Protein-based profiling of the human IgA1 clonal repertoire revealed shared clones of serum polymeric IgA1 and milk secretory IgA1. Cell Mol Immunol 2023; 20:305-307. [PMID: 36596872 PMCID: PMC9971200 DOI: 10.1038/s41423-022-00965-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 12/06/2022] [Indexed: 01/05/2023] Open
Grants
- R01 GM098539 NIGMS NIH HHS
- R01 AI149431 NIAID NIH HHS
- K01 DK106341 NIDDK NIH HHS
- R01 AI162236 NIAID NIH HHS
- R01 DK078244 NIDDK NIH HHS
- R01 DK082753 NIDDK NIH HHS
- R56 DK078244 NIDDK NIH HHS
- NIH: AI149431, GM098539, DK078244, DK082753, DK106341, and AI162236
- NIH: AI149431, GM098539, DK078244, DK082753, and AI162236
- NIH: DK106341
- NIH: AI149431, DK082753, DK106341
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Affiliation(s)
- Jan Novak
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Matthew B Renfrow
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - R Glenn King
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Colin Reily
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Todd J Green
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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9
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Dingess KA, Hoek M, van Rijswijk DMH, Tamara S, den Boer MA, Veth T, Damen MJA, Barendregt A, Romijn M, Juncker HG, van Keulen BJ, Vidarsson G, van Goudoever JB, Bondt A, Heck AJR. Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling. Cell Mol Immunol 2023; 20:26-37. [PMID: 36447030 PMCID: PMC9707141 DOI: 10.1038/s41423-022-00954-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 11/03/2022] [Indexed: 11/30/2022] Open
Abstract
The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.
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Affiliation(s)
- Kelly A Dingess
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Amsterdam UMC, Vrije Universiteit, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development Research Institute, Department of Pediatrics, Amsterdam, the Netherlands
| | - Max Hoek
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Danique M H van Rijswijk
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Sem Tamara
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Maurits A den Boer
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Tim Veth
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Mirjam J A Damen
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Arjan Barendregt
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Michelle Romijn
- Amsterdam UMC, Vrije Universiteit, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development Research Institute, Department of Pediatrics, Amsterdam, the Netherlands
| | - Hannah G Juncker
- Amsterdam UMC, Vrije Universiteit, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development Research Institute, Department of Pediatrics, Amsterdam, the Netherlands
| | - Britt J van Keulen
- Amsterdam UMC, Vrije Universiteit, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development Research Institute, Department of Pediatrics, Amsterdam, the Netherlands
| | - Gestur Vidarsson
- Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Johannes B van Goudoever
- Amsterdam UMC, Vrije Universiteit, University of Amsterdam, Emma Children's Hospital, Amsterdam Reproduction & Development Research Institute, Department of Pediatrics, Amsterdam, the Netherlands
| | - Albert Bondt
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands
| | - Albert J R Heck
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands.
- Netherlands Proteomics Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands.
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10
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Hassan Omer ZI, Lu J, Cheng YJ, Li PX, Chen ZH, Wang WH. Age-dependent changes in the anatomical and histological characteristics of the aggregated lymphoid nodules in the stomach of Dromedary camels (Camelus Dromedarius). PLoS One 2023; 18:e0279417. [PMID: 36947571 PMCID: PMC10032504 DOI: 10.1371/journal.pone.0279417] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 12/06/2022] [Indexed: 03/23/2023] Open
Abstract
Gastrointestinal associated lymphoid tissue (GALT) is an important component of the mucosal immune system. It is the largest mass of lymphoid tissues in the body and makes up more than 70% immune cells of entire body. GALT is considered to be the origin of systemic mucosal immunity and consists of solitary lymphoid nodules, aggregated lymphoid nodules (Peyer's patches, PPs), scattered lymphoid tissues, and follicular associated epithelia. PPs play important roles as antigen inductive sites of the mucosal immune system, which are mainly distributed in the intestine of animals and humans (especially ileum and appendix). However, a special area of well-developed aggregated lymphoid nodules in the abomasum of Dromedary camel was found in our laboratory. Its existence was rarely described in the stomach before. In the present study, we investigated this special structure with the dromedary camels of different ages (young, 0.5-2 years; pubertal, 3-5 years; middle-aged, 6-16 years; old, 17-20 years), by the anatomical, histological and immunohistochemical approaches. The results showed that the special structure was mainly distributed in the cardiac glandular area of the abomasum, forming a triangular area. The mucosal folds in this area were significantly thicker than those in the surrounding region. These mucosal folds had two different forms, namely reticular mucosal folds (RMF) and longitudinal mucosal folds (LMF). There were abundant lymphoid nodules in the submucosa of RMF and LMF, which were arranged in one or multiple rows. The statistical analysis of the height and thickness of RMF and LMF showed that the structure was most developed in pubertal dromedary camels. The histological characteristics of the structure were the same as PPs in the intestine of the Dromedary camel, while anatomical appearance showed some difference. The immunohistochemical examination revealed that both immunoglobulin A (IgA) and G (IgG) antibodies-producing cells (APCs) were extensively distributed in the gastric lamina propria (LP) in all age group. Our finding suggest that camel stomach not only performs digestive functions, but also involves parts of body immunity.
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Affiliation(s)
| | - Jia Lu
- Department of pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Yu-Jiao Cheng
- Department of pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Pei-Xuan Li
- Department of pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Zhi-Hua Chen
- Department of pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Wen-Hui Wang
- Department of pathology, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
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11
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Zhai K, Zhang Z, Liu X, Lv J, Zhang L, Li J, Ma Z, Wang Y, Guo H, Zhang Y, Pan L. Mucosal immune responses induced by oral administration of recombinant Lactococcus lactis expressing the S1 protein of PDCoV. Virology 2023; 578:180-189. [PMID: 36586181 DOI: 10.1016/j.virol.2022.12.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/20/2022] [Accepted: 12/20/2022] [Indexed: 12/27/2022]
Abstract
Porcine deltacoronavirus is an evolving coronavirus that primarily infects the intestine and may lead to intestinal disease in piglets. Up to now, no commercial vaccination is readily accessible to protect against the spread of PDCoV. Lactococcus lactis has been shown to have good immune efficacy and safety and can be used as a genetically engineered vaccine to deliver antigens. In this research, we utilized L. lactis NZ9000 to provide the S1 protein orally and improved the delivery efficiency by connecting the M cell targeting ligand Co1 with the S1 protein of PDCoV in tandem to obtain the recombinant protein S1-Co1. We successfully constructed two recombinant strains capable of expressing PDCoV-S1 and PDCoV-S1-Co1 proteins (i.e., L. lactis NZ9000-S1 and L. lactis NZ9000-S1-Co1), and their immunogenic capacity was evaluated in mice. Our study shows that Lactococcus is an advantageous bacterial live vector vaccine and is anticipated as a potential PDCoV vaccination option.
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Affiliation(s)
- Kaige Zhai
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Zhongwang Zhang
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Xinsheng Liu
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Jianliang Lv
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Liping Zhang
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Jiahao Li
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Zhongyuan Ma
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Yonglu Wang
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Huichen Guo
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Yongguang Zhang
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
| | - Li Pan
- State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
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12
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Mucosal Immune System Dysregulation in the Pathogenesis of IgA Nephropathy. Biomedicines 2022; 10:biomedicines10123027. [PMID: 36551783 PMCID: PMC9775168 DOI: 10.3390/biomedicines10123027] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 11/25/2022] Open
Abstract
The mucosal immune system, via a dynamic immune network, serves as the first line of defense against exogenous antigens. Mucosal immune system dysregulation is closely associated with the pathogenesis of immunoglobulin A nephropathy (IgAN), as illustrated by IgAN having the clinical feature of gross hematuria, often concurrent with mucosal infections. Notably, previous studies have demonstrated the efficacy of tonsillectomy and found that a targeted-release formulation of budesonide reduced proteinuria in patients with IgAN. However, it remains unclear how exogenous antigens interact with the mucosal immune system to induce or exacerbate IgAN. Thus, in this review, we focus on the dysregulation of mucosal immune response in the pathogenesis of IgAN.
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Castellanos-Huerta I, Gómez-Verduzco G, Tellez-Isaias G, Ayora-Talavera G, Bañuelos-Hernández B, Petrone-García VM, Fernández-Siurob I, Velázquez-Juárez G. Immune Evaluation of Avian Influenza Virus HAr Protein Expressed in Dunaliella salina in the Mucosa of Chicken. Vaccines (Basel) 2022; 10:vaccines10091418. [PMID: 36146496 PMCID: PMC9505873 DOI: 10.3390/vaccines10091418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/15/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Avian influenza (AI) is a serious threat to the poultry industry worldwide. Currently, vaccination efforts are based on inactivated, live attenuated, and recombinant vaccines, where the principal focus is on the type of virus hemagglutinin (HA), and the proposed use of recombinant proteins of AI virus (AIV). The use of antigens produced in microalgae is a novel strategy for the induction of an immune response in the mucosal tissue. The capacity of the immune system in poultry, particularly in mucosa, plays an important role in the defense against pathogens. This system depends on a complex relationship between specialized cells and soluble factors, which confer protection against pathogens. Primary lymphoid organs (PLO), as well as lymphocytic aggregates (LA) such as the Harderian gland (HG) and mucosa-associated lymphoid tissue (MALT), actively participate in a local immune response which is mainly secretory IgA (S-IgA). This study demonstrates the usefulness of subunit antigens for the induction of a local and systemic immune response in poultry via ocular application. These findings suggest that a complex protein such as HAr from AIV (H5N2) can successfully induce increased local production of S-IgA and a specific systemic immune response in chickens.
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Affiliation(s)
- Inkar Castellanos-Huerta
- Programa de Maestría y Doctorado en Ciencias de la Producción y de la Salud Animal, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de Mexico 04510, Mexico
| | - Gabriela Gómez-Verduzco
- Departamento de Medicina y Zootecnia de Aves, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Ciudad de Mexico 04510, Mexico
| | | | - Guadalupe Ayora-Talavera
- Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autonoma de Yucatan (UADY), Merida 97000, Yucatan, Mexico
| | - Bernardo Bañuelos-Hernández
- Escuela de Veterinaria, Universidad De La Salle Bajío, Avenida Universidad 602, Lomas del Campestre, Leon 37150, Guanajuato, Mexico
| | - Víctor Manuel Petrone-García
- Departamento de Ciencias Pecuarias, Facultad de Estudios Superiores Cuautitlán UNAM, Cuautitlan 54714, Mexico
- Correspondence:
| | | | - Gilberto Velázquez-Juárez
- Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Boulevard Marcelino Garcia Barragan #1421, Guadalajara 44430, Jalisco, Mexico
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14
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Zhang X, Jiang G, Ji C, Fan Z, Ge S, Li H, Wang Y, Lv X, Zhao F. Comparative Whey Proteome Profiling of Donkey Milk With Human and Cow Milk. Front Nutr 2022; 9:911454. [PMID: 35845789 PMCID: PMC9282231 DOI: 10.3389/fnut.2022.911454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
Donkey milk (DM), similar to human milk (HM) in chemical composition, has been suggested as the best potential hypoallergenic replacement diet for babies suffering from Cow milk (CM) protein allergy. In order to better understand DM protein, many studies based on proteomic have been performed. In this study, the label-free quantitative proteomic approach was conducted to quantitatively identify the differentially expressed whey proteins (DEPs) in DM vs. HM group and DM vs. CM group. In total, 241 and 365 DEPs were found in these two groups, respectively. Bioinformatics analysis of DEPs showed that the majority of DEPs participated in the lipoprotein metabolic process, regulation of cytokine production, chemical homeostasis, and catabolic process. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways analysis found that these DEPs mainly participated in an antigen processing, complement, and coagulation cascades. These results may provide valuable information in the composition of milk whey proteins in DM, HM, and CM, especially for low abundant components, and expand our knowledge of different biological functions between DM and HM or CM.
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Affiliation(s)
- Xinhao Zhang
- Department of Animal Pharmacy, College of Pharmacy, Heze University, Heze, China
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Guimiao Jiang
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Chuanliang Ji
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Zhaobin Fan
- Department of Animal Pharmacy, College of Pharmacy, Heze University, Heze, China
| | - Shihao Ge
- Department of Animal Pharmacy, College of Pharmacy, Heze University, Heze, China
| | - Haijing Li
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Yantao Wang
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Xin Lv
- National Engineering Research Center for Gelatin-Based TCM, Dong-E E-Jiao Co., Ltd., Liaocheng, China
| | - Fuwei Zhao
- Department of Animal Pharmacy, College of Pharmacy, Heze University, Heze, China
- *Correspondence: Fuwei Zhao
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15
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Kim JY, Bang SJ, Kim JY, Choi EJ, Heo K, Shim JJ, Lee JL. The Probiotic Strain Bifidobacterium animalis ssp. lactis HY8002 Potentially Improves the Mucosal Integrity of an Altered Intestinal Microbial Environment. Front Microbiol 2022; 13:817591. [PMID: 35572671 PMCID: PMC9102380 DOI: 10.3389/fmicb.2022.817591] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 04/11/2022] [Indexed: 11/13/2022] Open
Abstract
Intestinal microbiota mediate the development and regulation of the intestinal immune system either directly or indirectly. Particularly, Bifidobacterium spp. play an important role in regulating the intestinal immunity and intestinal barrier. We demonstrated that Bifidobacterium animalis ssp. lactis HY8002, selected from eight Bifidobacterium strains by in vitro experimentation, had exceptional resistance to digestive tract conditions and high adhesion to intestinal epithelial cells and a positive effect on immunoglobulin A (IgA) secretion by Peyer’s patch cells. Moreover, HY8002 restored the expression of tight junction-related genes, initially reduced by lipopolysaccharide treatment, to normal levels in human intestinal epithelial cells. Notably, HY8002 restored kanamycin-induced reduction in Peyer’s patch cell numbers, serum and fecal IgA levels, and zonula occludens 1 and Toll-like receptor 2 levels in the mouse small intestine. In addition, HY8002 restores microbiome composition disturbed by kanamycin, and these microbiome changes have been found to correlate with TLR2 levels in the small intestine. Moreover, the ability of HY8002 to enhance IgA in Peyer’s patch cells and ZO-1 levels in intestinal epithelial cells was significantly inhibited by a TLR2 blocking antibody, which suggests that the HY8002 improve intestinal barrier function via TLR2. Finally, whole-genome sequencing of HY8002 revealed that it did not possess any known virulence factors. Therefore, HY8002 is a promising, functional probiotic supplement to improve intestinal barrier function by improving intestinal immunity and microbiota balance.
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16
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Nagasawa Y, Misaki T, Ito S, Naka S, Wato K, Nomura R, Matsumoto-Nakano M, Nakano K. Title IgA Nephropathy and Oral Bacterial Species Related to Dental Caries and Periodontitis. Int J Mol Sci 2022; 23:725. [PMID: 35054910 PMCID: PMC8775524 DOI: 10.3390/ijms23020725] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 12/23/2022] Open
Abstract
A relationship between IgA nephropathy (IgAN) and bacterial infection has been suspected. As IgAN is a chronic disease, bacteria that could cause chronic infection in oral areas might be pathogenetic bacteria candidates. Oral bacterial species related to dental caries and periodontitis should be candidates because these bacteria are well known to be pathogenic in chronic dental disease. Recently, several reports have indicated that collagen-binding protein (cnm)-(+) Streptococcs mutans is relate to the incidence of IgAN and the progression of IgAN. Among periodontal bacteria, Treponema denticola, Porphyromonas gingivalis and Campylobacte rectus were found to be related to the incidence of IgAN. These bacteria can cause IgAN-like histological findings in animal models. While the connection between oral bacterial infection, such as infection with S. mutans and periodontal bacteria, and the incidence of IgAN remains unclear, these bacterial infections might cause aberrantly glycosylated IgA1 in nasopharynx-associated lymphoid tissue, which has been reported to cause IgA deposition in mesangial areas in glomeruli, probably through the alteration of microRNAs related to the expression of glycosylation enzymes. The roles of other factors related to the incidence and progression of IgA, such as genes and cigarette smoking, can also be explained from the perspective of the relationship between these factors and oral bacteria. This review summarizes the relationship between IgAN and oral bacteria, such as cnm-(+) S. mutans and periodontal bacteria.
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Affiliation(s)
- Yasuyuki Nagasawa
- Department of General Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan
| | - Taro Misaki
- Division of Nephrology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, Shizuoka, Japan;
- Department of Nursing, Faculty of Nursing, Seirei Christopher University, Hamamatsu 433-8558, Shizuoka, Japan
| | - Seigo Ito
- Department of Internal Medicine, Japan Self-Defense Gifu Hospital, Kakamigahara 502-0817, Gifu, Japan;
| | - Shuhei Naka
- Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Okayama, Japan; (S.N.); (M.M.-N.)
| | - Kaoruko Wato
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
| | - Ryota Nomura
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
| | - Michiyo Matsumoto-Nakano
- Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Okayama, Japan; (S.N.); (M.M.-N.)
| | - Kazuhiko Nakano
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
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17
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Raderer M, Kiesewetter B. What you always wanted to know about gastric MALT-lymphoma: a focus on recent developments. Ther Adv Med Oncol 2021; 13:17588359211033825. [PMID: 34621332 PMCID: PMC8491302 DOI: 10.1177/17588359211033825] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 12/17/2022] Open
Abstract
The stomach is the most common site of origin for extranodal lymphomas,
with extranodal marginal zone B-cell of the mucosa associated lymphoid
tissue (MALT-lymphoma) being the predominant subtype. MALT-lymphoma
develops in mucosa associated lymphoid structures acquired by
infection or chronic antigenic stimuli and may therefore arise in
almost any organ of the human body. In spite of histopathologic
similarities between various organs upon first glance, recent findings
suggest pronounced differences between different sites, with a variety
of features specific to gastric MALT-lymphoma. The objective of this
review is to sum up the current knowledge on pathogenesis, molecular
pathology, clinical presentation and therapeutic approaches to gastric
MALT-lymphoma with in-depth discussion of recent developments.
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Affiliation(s)
- Markus Raderer
- Division of Oncology, Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18 - 20, Vienna, A 1090, Austria
| | - Barbara Kiesewetter
- Division of Oncology, Internal Medicine I, Medical University of Vienna, Vienna, Austria
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18
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Zhang X, Jiang B, Ji C, Li H, Yang L, Jiang G, Wang Y, Liu G, Liu G, Min L, Zhao F. Quantitative Label-Free Proteomic Analysis of Milk Fat Globule Membrane in Donkey and Human Milk. Front Nutr 2021; 8:670099. [PMID: 34239890 PMCID: PMC8258387 DOI: 10.3389/fnut.2021.670099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/21/2021] [Indexed: 12/11/2022] Open
Abstract
Previous studies have found donkey milk (DM) has the similar compositions with human milk (HM) and could be used as a potential hypoallergenic replacement diet for babies suffering from cow's milk allergy. Milk fat globule membrane (MFGM) proteins are involved in many biological functions, behaving as important indicators of the nutritional quality of milk. In this study, we used label-free proteomics to quantify the differentially expressed MFGM proteins (DEP) between DM (in 4-5 months of lactation) and HM (in 6-8 months of lactation). In total, 293 DEP were found in these two groups. Gene Ontology (GO) enrichment analysis revealed that the majority of DEP participated in regulation of immune system process, membrane invagination and lymphocyte activation. Several significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined for the DEP, such as lysosome, galactose metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study may provide valuable information in the composition of MFGM proteins in DM and HM, and expand our knowledge of different biological functions between DM and HM.
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Affiliation(s)
- Xinhao Zhang
- College of Animal Science and Technology, Shandong Agricultural University, Taian, China.,National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Bo Jiang
- Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agricultural and Forestry Sciences, Beijing, China
| | - Chuanliang Ji
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Haijing Li
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Li Yang
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Guimiao Jiang
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Yantao Wang
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Guangyuan Liu
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
| | - Guiqin Liu
- Shandong Donkey Industry, Technology Collaborative Innovation Center, Liaocheng University, Liaocheng, China
| | - Lingjiang Min
- College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China
| | - Fuwei Zhao
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E E-Jiao Co., Ltd, Liaocheng, China
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19
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Ouyang W, Wu Y, Lin X, Wang S, Yang Y, Tang L, Liu Z, Wu J, Huang C, Zhou Y, Zhang X, Hu J, Liu Z. Role of CD4+ T Helper Cells in the Development of BAC-Induced Dry Eye Syndrome in Mice. Invest Ophthalmol Vis Sci 2021; 62:25. [PMID: 33492357 PMCID: PMC7838551 DOI: 10.1167/iovs.62.1.25] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Purpose To evaluate the role of CD4+ T helper cells in benzalkonium chloride (BAC)-induced ocular surface disorder in C57BL/6 mice. Methods Topical 0.075% BAC was applied twice daily in C57BL/6 mice for 7 consecutive days; PBS-treated and untreated mice served as controls. Adoptive transfer of CD4+ T cells isolated from the BAC-treated mice or PBS-treated mice into nude mice was conducted to identify the roles of CD4+ T cells, with untreated nude mice as controls. Oregon green dextran staining, PAS staining, and the phenol red cotton test were carried out in these two models. The gene and protein levels of T-bet, IFN-γ, RORγt, and IL-17 were detected by quantitative RT-PCR and ELISA, respectively. The activation and subsets of CD4+ T cells were identified by double immunofluorescent staining and flow cytometry. Results An increase in CD4+CD69+, CD4+IFN-γ+, and CD4+IL-17+ cells was induced by BAC in C57BL/6 mice. IFN-γ, IL-17, Th1, Th17, and the transcription factors T-bet and RORγt were increased in BAC-treated mice compared with control mice. In addition, ocular surface damage, including corneal barrier dysfunction, goblet cell loss, and decreased tear production, was induced by BAC. Interestingly, adoptive transfer of CD4+ T cells isolated from BAC-treated mice into nude mice resulted in ocular surface manifestations similar to those of direct topical BAC treatment of C57BL/6 mice, including increased CD4+ T cells, IFN-γ, IL-17, and ocular surface disorders. Conclusions Topical application of BAC induced a dry-eye-like ocular surface disorder partly through the CD4+ T cell-mediated inflammatory response.
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Affiliation(s)
- Weijie Ouyang
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Yang Wu
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.,Department of Ophthalmology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China
| | - Xiang Lin
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Shoubi Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yiran Yang
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Liying Tang
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Zhaolin Liu
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jieli Wu
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Caihong Huang
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Yueping Zhou
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Xiaobo Zhang
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jiaoyue Hu
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.,Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China
| | - Zuguo Liu
- Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.,Xiamen University Affiliated Xiamen Eye Center, Xiamen, Fujian, China
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20
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Akbari Fard L, Zehsaz F, Farhangi N. Concurrent exercise training effect on salivary immunoglobulin A and alpha-amylase in children with cerebral palsy. GERMAN JOURNAL OF EXERCISE AND SPORT RESEARCH 2021. [DOI: 10.1007/s12662-020-00696-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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21
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The CH1α domain of mucosal gp41 IgA contributes to antibody specificity and antiviral functions in HIV-1 highly exposed Sero-Negative individuals. PLoS Pathog 2020; 16:e1009103. [PMID: 33315937 PMCID: PMC7802955 DOI: 10.1371/journal.ppat.1009103] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 01/12/2021] [Accepted: 10/26/2020] [Indexed: 01/22/2023] Open
Abstract
The antibody molecule comprises a variable domain conferring antigen specificity and affinity distinct from the heavy chain constant (CH) domains dictating effector functions. We here interrogate this paradigm by evaluating the unique influence of the CH1α domain on epitope specificity and functions using two mucosal gp41-specific Fab-IgAs (FabA) derived from HIV-1 highly-exposed but persistently seronegative individuals (HESN). These HESN develop selectively affinity-matured HIV-1-specific mucosal IgA that target the gp41 viral envelope and might provide protection although by unclear mechanisms. Isotype-switching FabAs into Fab-IgGs (FabGs) results in a >10-fold loss in affinity for HIV-1 clade A, B, and C gp41, together with reduced neutralization of HIV-1 cross-clade. The FabA conformational epitopes map selectively on gp41 in 6-Helix bundle and pre-fusion conformations cross-clade, unlike FabGs. Finally, we designed in silico, a 12 amino-acid peptide recapitulating one FabA conformational epitope that inhibits the FabA binding to gp41 cross-clade and its neutralizing activity. Altogether, our results reveal that the CH1α domain shapes the antibody paratope through an allosteric effect, thereby strengthening the antibody specificity and functional activities. Further, they clarify the mechanisms by which these HESN IgAs might confer protection against HIV-1-sexual acquisition. The IgA-specific epitope we characterized by reverse vaccinology could help designing a mucosal HIV-1 vaccine.
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Mboumba Bouassa RS, Péré H, Jenabian MA, Veyer D, Meye JF, Touzé A, Bélec L. Natural and vaccine-induced B cell-derived systemic and mucosal humoral immunity to human papillomavirus. Expert Rev Anti Infect Ther 2020; 18:579-607. [PMID: 32242472 DOI: 10.1080/14787210.2020.1750950] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Human papillomavirus (HPV) are the causative agent of mucosal neoplasia. Both cervical, anal and oropharyngeal cancers incidence is constantly increasing, making the HPV infection, a significant worldwide concern. Together, the CD8+ T cytotoxic cell-mediated response and the HPV-specific antibody response control most of the HPV infections before the development of cancers.Areas covered: We searched the MEDLINE and EMBASE databases and identified 228 eligible studies from 1987 to 2019 which examines both naturally acquired and vaccine induced humoral immunity against HPV infection in female and male subjects from worldwide origin. Herein, we synthesize current knowledge on the features of systemic and mucosal humoral immunity against HPV. We discuss the issues of the balance between the viral clearance or the escape to the host immune response, the differences between natural and vaccine-induced HPV-specific antibodies and their neutralizing capability. We also discuss the protection afforded after natural infection or following prophylactic vaccination.Expert opinion: Understanding the antibody response induced by HPV infection has led to the design of first-generation prophylactic vaccines. Now, prophylactic vaccination induces protective and long-lasting antibody response which would also strengthened the natural moderate humoral response in people previously exposed to the virus.
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Affiliation(s)
- Ralph-Sydney Mboumba Bouassa
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,Laboratoire de virologie, Ecole Doctorale Régionale En Infectiologie Tropicale, Franceville, Gabon.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France
| | - Hélène Péré
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Faculté de Médecine, Université Paris Descartes, Paris, France
| | - Mohammad-Ali Jenabian
- Département Des Sciences Biologiques Et Centre De Recherche BioMed, Université Du Québec À Montréal (UQAM), Montreal, QC, Canada
| | - David Veyer
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France
| | - Jean-François Meye
- Service De Gynécologie Obstétrique, Centre Hospitalo-Universitaire d'Agondjé Et Faculté De Médecine De Libreville, Université Des Sciences De La Santé, Libreville, Gabon
| | - Antoine Touzé
- UMRINRA ISP 1282, Equipe Biologie Des Infections À Polyomavirus, Université De Tours, Tours, France
| | - Laurent Bélec
- Laboratoire De Virologie, Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.,INSERM UMR U970 (Immunothérapie Et Traitement Anti-angiogénique En cancérologie), Paris Centre De Recherche Cardiovasculaire (PARCC), Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Faculté de Médecine, Université Paris Descartes, Paris, France
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Abstract
Many studies highlighted that a bidirectional communication between the gut and the central nervous system (CNS) exists. A vigorous immune response to antigens must be avoided, and pathogenic organisms crossing the gut barrier must be detected and killed. For this reason, the immune system developed fine mechanisms able to maintain this delicate balance. The microbiota is beneficial to its host, providing protection against pathogenic bacteria. It is intimately involved in numerous aspects of host physiology, from nutritional status to behavior and stress response. In the last few years, the implication of the gut microbiota and its bioactive microbiota-derived molecules in the progression of multiple diseases, as well as in the development of neurodegenerative disorders, gained increasing attention. The purpose of this review is to provide an overview of the gut microbiota with particular attention toward neurological disorders and mast cells. Relevant roles are played by the mast cells in neuroimmune communication, such as sensors and effectors of cytokines and neurotransmitters. In this context, the intake of beneficial bacterial strains as probiotics could represent a valuable therapeutic approach to adopt in combination with classical therapies. Further studies need to be performed to understand if the gut bacteria are responsible for neurological disorders or if neurological disorders influence the bacterial profile.
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Fischer T, Klinger A, von Smolinski D, Orzekowsky-Schroeder R, Nitzsche F, Bölke T, Vogel A, Hüttmann G, Gebert A. High-resolution imaging of living gut mucosa: lymphocyte clusters beneath intestinal M cells are highly dynamic structures. Cell Tissue Res 2020; 380:539-546. [PMID: 31970486 DOI: 10.1007/s00441-020-03167-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/06/2020] [Indexed: 10/25/2022]
Abstract
In the Peyer's patches of the small intestine, specialized epithelial cells, the membranous (M) cells, sample antigenic matter from the gut lumen and bring it into contact with cells of the immune system, which are then capable of initiating specific immune reactions. Using autofluorescence 2-photon (A2P) microscopy, we imaged living intestinal mucosa at a 0.5-μm resolution. We identified individual M cells without the aid of a marker and in vivo analyzed their sampling function over hours. Time-lapse recordings revealed that lymphocytes associated with M cells display a remarkable degree of motility with average speed rates of 8.2 μm/min, to form new M cell-associated lymphocyte clusters within less than 15 min. The lymphocytes drastically deform the M cells' cytoplasm and laterally move from one lymphocyte cluster to the next. This implies that the micro-compartment beneath M cells is a highly efficient container to bring potentially harmful antigens into contact with large numbers of immunocompetent cells. Our setup opens a new window for high-resolution 3D imaging of functional processes occurring in lymphoid and mucosal tissues.
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Affiliation(s)
- Tobias Fischer
- Institute of Anatomy II, University Hospital Jena, Teichgraben 7, 07743, Jena, Germany.
| | - Antje Klinger
- Institute of Anatomy, University of Luebeck, Luebeck, Germany
| | | | | | - Falk Nitzsche
- Institute of Anatomy II, University Hospital Jena, Teichgraben 7, 07743, Jena, Germany
| | - Torsten Bölke
- Institute of Anatomy II, University Hospital Jena, Teichgraben 7, 07743, Jena, Germany
| | - Alfred Vogel
- Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
| | - Gereon Hüttmann
- Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
| | - Andreas Gebert
- Institute of Anatomy II, University Hospital Jena, Teichgraben 7, 07743, Jena, Germany.,Institute of Anatomy, University of Luebeck, Luebeck, Germany
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Abstract
The skin is the outermost organ of the body and is exposed to many kinds of external pathogens. To manage this, the skin contains multiple types of immune cells. To achieve sufficient induction of cutaneous adaptive immune responses, the antigen presentation/recognition in the skin is an essential process. Recent studies have expanded our knowledge of how T cells survey their cognate antigens in the skin. In addition, the formation of a lymphoid cluster, named inducible skin-associated lymphoid tissue (iSALT), has been reported during skin inflammation. Although iSALT may not be classified as a typical tertiary lymphoid organ, it provides specific antigen presentation sites in the skin. In this article, we provide an overview of the antigen presentation mechanism in the skin, with a focus on the development of iSALT and its function.
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Affiliation(s)
- Gyohei Egawa
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Suzuki K. Diversified IgA-Bacteria Interaction in Gut Homeostasis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1254:105-116. [PMID: 32323273 DOI: 10.1007/978-981-15-3532-1_9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Immunoglobulin A (IgA) is the major immunoglobulin isotype produced by the gut immune system, and many studies revealed key roles of IgA in establishing host-bacteria mutualism. This chapter will review current understandings for the function of gut IgA in regulating commensal microbiota. IgA specifically recognizes bacterial species that strongly stimulate host's immune responses, and suppresses their overgrowth or reduces the expressions of bacterial pro-inflammatory genes. On the other hand, IgA coatings on symbiotic bacteria enhance bacteria-mucus and bacteria-bacteria interactions, which induce production of metabolites enforcing mucosal barrier functions. Such diversified effects suggest that multiple factors may be involved in the mechanisms of IgA-bacteria interactions, including IgA specificity to microbial epitopes, mode of cellular responses of IgA synthesis (T-dependent and T-independent) and post-translational modifications of IgA proteins, such as glycosylation.
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Affiliation(s)
- Keiichiro Suzuki
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS), RIKEN, 1-7-22 Suehiro-Cho, Tsurumi-Ku Yokohama, 230-0045, Kanagawa, Japan.
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27
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Sánchez-Salguero E, Mondragón-Ramírez GK, Alcántara-Montiel JC, Cérbulo-Vázquez A, Villegas-Domínguez X, Contreras-Vargas VM, Thompson-Bonilla MDR, Romero-Ramírez H, Santos-Argumedo L. Infectious episodes during pregnancy, at particular mucosal sites, increase specific IgA1 or IgA2 subtype levels in human colostrum. Matern Health Neonatol Perinatol 2019; 5:9. [PMID: 31205733 PMCID: PMC6558797 DOI: 10.1186/s40748-019-0104-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 05/12/2019] [Indexed: 12/14/2022] Open
Abstract
Background Colostrum is the primary source of maternal immunoglobulin A (IgA) for the newborn. IgA participates in protection and regulation mechanisms of the immune response at the neonate’s mucosa. Several studies have evaluated infectious diseases and vaccine protocols effects during pregnancy on maternal milk IgA levels, with the aim to understand lactation protecting effect on newborn. However, most of their results demonstrated that there were no differences in the total IgA levels. In humans, IgA has two subclasses (IgA1 and IgA2), they have an anatomical distribution among mucosal compartments, their levels vary after antigen stimulation and are also seen to describe differential affinities in colostrum. Although there are differences between IgA subclasses in several compartments, these studies have excluded specific colostrum IgA1 and IgA2 determination. Methods We analyzed data from 900 women in Mexico City. With Pearson correlation, we compared the number of infectious episodes during their pregnancy that was associated with mucosal compartments (skin, respiratory and gastrointestinal tracts) and colostrum IgA subclasses. Results We show a correlation between increased colostrum IgA1 levels and the number of infectious episodes at respiratory tract and the skin. In contrast, infections at the gastrointestinal tract correlated with increased IgA2 amounts. Conclusions Infections present during pregnancy at certain mucosal site increase specific IgA subclasses levels in human colostrum. These results will help in understanding infections and immunizations effects on maternal IgA at the mammary gland, and their impact on the development and protection of the newborn. Electronic supplementary material The online version of this article (10.1186/s40748-019-0104-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Erick Sánchez-Salguero
- 1Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV), National Polytechnic Institute (IPN), Mexico City, Mexico
| | - Geovanni Kaleb Mondragón-Ramírez
- 1Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV), National Polytechnic Institute (IPN), Mexico City, Mexico.,2Interdisciplinary Center for Health Sciences, Milpa Alta Unit (CICSUMA), National Polytechnic Institute (IPN), Mexico City, Mexico
| | - Julio C Alcántara-Montiel
- School of Higher Studies Zaragoza, National Autonomous University of Mexico (UNAM), Regional Hospital of High Specialty of Ixtapaluca (HRAEI), Mexico City, Mexico
| | - Arturo Cérbulo-Vázquez
- 4Faculty of Medicine, Plan of Combined Studies in Medicine (PECEM), National Autonomous University of Mexico (UNAM), Mexico City, Mexico.,5Women's Hospital, Ministry of Health (SSA), Mexico City, Mexico
| | | | - Víctor Manuel Contreras-Vargas
- 6Departments of Gynecology and Genomic Medicine, Regional Hospital 1° de Octubre, Institute of Security and Social Services of State Workers (ISSSTE), Mexico City, Mexico
| | - María Del Rocío Thompson-Bonilla
- 6Departments of Gynecology and Genomic Medicine, Regional Hospital 1° de Octubre, Institute of Security and Social Services of State Workers (ISSSTE), Mexico City, Mexico
| | - Héctor Romero-Ramírez
- 1Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV), National Polytechnic Institute (IPN), Mexico City, Mexico
| | - Leopoldo Santos-Argumedo
- 1Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV), National Polytechnic Institute (IPN), Mexico City, Mexico
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Jones AW, Davison G. Exercise, Immunity, and Illness. MUSCLE AND EXERCISE PHYSIOLOGY 2019. [PMCID: PMC7149380 DOI: 10.1016/b978-0-12-814593-7.00015-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
It is generally accepted that moderate amounts of exercise improve immune system functions and hence reduce the risk of infection whereas athletes engaged in regular prolonged and/or intensive training have a higher than “normal” incidence of minor infections, especially of the upper respiratory tract (URT, e.g., common cold and influenza). This is likely related to regular acute (and possibly chronic) periods of exercise-induced changes in immune function. URT infections can compromise performance directly if suffered shortly before or during competition or indirectly if suffered at other times via effects on training and/or physiological adaptations. This chapter covers the effects of exercise (acute and chronic), both positive and negative, on immune function and consequent infection risk, and considers the current state-of-the-art for monitoring and assessing this in athletes.
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Ladel S, Flamm J, Zadeh AS, Filzwieser D, Walter JC, Schlossbauer P, Kinscherf R, Lischka K, Luksch H, Schindowski K. Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery? Pharmaceutics 2018; 10:pharmaceutics10030107. [PMID: 30050027 PMCID: PMC6161100 DOI: 10.3390/pharmaceutics10030107] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 07/19/2018] [Accepted: 07/20/2018] [Indexed: 12/24/2022] Open
Abstract
Background: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery. Methods: Immunoreactivity and messenger RNA (mRNA) expression of FcRn was determined in ex vivo porcine olfactory mucosa. Uptake of IgG was performed in a side-by-side cell and analysed by immunofluorescence. Results: FcRn was found in epithelial and basal cells of the olfactory epithelium as well as in glands, cavernous bodies and blood vessels. Allogenic porcine IgGs were found time-dependently in the lamina propria and along axonal bundles, while only small amounts of xenogenic human IgGs were detected. Interestingly, lymphoid follicles were spared from allogenic IgGs. Conclusion: Fc-mediated transport of IgG across the nasal epithelial barrier may have significant potential for intranasal delivery, but the relevance of immune interaction in lymphoid follicles must be clarified to avoid immunogenicity.
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Affiliation(s)
- Simone Ladel
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
- Faculty for Natural Sciences, University of Ulm, 89081 Ulm, Germany.
| | - Johannes Flamm
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
- Faculty for Natural Sciences, University of Ulm, 89081 Ulm, Germany.
| | - Arghavan Soleimani Zadeh
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
- Faculty for Natural Sciences, University of Ulm, 89081 Ulm, Germany.
- Faculty of Medicine, Graduate School 'Molecular Medicine', University of Ulm, 89081 Ulm, Germany.
| | - Dorothea Filzwieser
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
| | - Julia-Christina Walter
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
- Faculty for Natural Sciences, University of Ulm, 89081 Ulm, Germany.
| | - Patrick Schlossbauer
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
| | - Ralf Kinscherf
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Philipps-University Marburg, 35032 Marburg, Germany.
| | - Katharina Lischka
- Chair of Zoology, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.
| | - Harald Luksch
- Chair of Zoology, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.
| | - Katharina Schindowski
- Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
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31
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Mohan T, Deng L, Wang BZ. CCL28 chemokine: An anchoring point bridging innate and adaptive immunity. Int Immunopharmacol 2017; 51:165-170. [PMID: 28843907 PMCID: PMC5755716 DOI: 10.1016/j.intimp.2017.08.012] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 07/31/2017] [Accepted: 08/15/2017] [Indexed: 11/18/2022]
Abstract
Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the body. CCL28, β- or CC chemokine, is involved in the host immunity at various epithelial and mucosal linings. The unique roles of CCL28 in several facets of immune responses have attracted considerable attention and may represent a promising approach to combat various infections. CCL28 displays a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi. Here, we will summarize various research findings regarding the antimicrobial activity of CCL28 and the relevant mechanisms behind it. We will explore how the structure of CCL28 is involved with this activity and how this function may have evolved. CCL28 displays strong homing capabilities for B and T cells at several mucosal and epithelial sites, and orchestrates the trafficking and functioning of lymphocytes. The chemotactic and immunomodulatory features of CCL28 through the interactions with its chemokine receptors, CCR10 and CCR3, will also be discussed in detail. Thus, in this review, we emphasize the dual properties of CCL28 and suggest its role as an anchoring point bridging the innate and adaptive immunity.
Chemokines play a vital role in cell migration in response to a chemical gradient by a process known as chemotaxis. CCL28 is a β- or CC chemokine that is involved in host immunity through the interactions with its chemokine receptors, CCR10 and CCR3. CCL28 is constitutively expressed in a wide variety of tissues including exocrine glands and is inducible through inflammation and infections. CCL28 has been shown to exhibit broad spectrum antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and some fungi. CCL28 displays strong homing capabilities for B and T cells and orchestrates the trafficking and functioning of lymphocytes. In this review, we emphasize the antimicrobial and immunomodulatory feature of CCL28 and its role as bridge between innate and adaptive immunity.
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Affiliation(s)
- Teena Mohan
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave, SE, Atlanta, GA 30303, USA
| | - Lei Deng
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave, SE, Atlanta, GA 30303, USA
| | - Bao-Zhong Wang
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave, SE, Atlanta, GA 30303, USA.
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Zhang W, Feng Q, Wang C, Zeng X, Du Y, Lin L, Wu J, Fu L, Yang K, Xu X, Xu H, Zhao Y, Li X, Schoenauer UH, Stadlmayr A, Saksena NK, Tilg H, Datz C, Liu X. Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma. THE JOURNAL OF IMMUNOLOGY 2017; 198:3719-3728. [DOI: 10.4049/jimmunol.1602039] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 02/23/2017] [Indexed: 01/10/2023]
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Scaramuzzi K, Tanaka GD, Neto FM, Garcia PR, Gabrili JJ, Oliveira DC, Tambourgi DV, Mussalem JS, Paixão-Cavalcante D, D’Azeredo Orlando MT, Botosso VF, Oliveira CL, Fantini MC, Sant’Anna OA. Nanostructured SBA-15 silica: An effective protective vehicle to oral hepatitis B vaccine immunization. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2016; 12:2241-2250. [DOI: 10.1016/j.nano.2016.06.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 05/10/2016] [Accepted: 06/08/2016] [Indexed: 11/28/2022]
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Sepahi A, Casadei E, Tacchi L, Muñoz P, LaPatra SE, Salinas I. Tissue Microenvironments in the Nasal Epithelium of Rainbow Trout (Oncorhynchus mykiss) Define Two Distinct CD8α+ Cell Populations and Establish Regional Immunity. THE JOURNAL OF IMMUNOLOGY 2016; 197:4453-4463. [PMID: 27798156 DOI: 10.4049/jimmunol.1600678] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 09/29/2016] [Indexed: 12/17/2022]
Abstract
Mucosal surfaces require balancing different physiological roles and immune functions. To effectively achieve multifunctionality, mucosal epithelia have evolved unique microenvironments that create unique regional immune responses without impairing other normal physiological functions. Whereas examples of regional immunity are known in other mucosal epithelia, to date, no immune microenvironments have been described in the nasal mucosa, a site where the complex functions of olfaction and immunity need to be orchestrated. In this study we identified the presence of CD8α+ cells in the rainbow trout (Oncorhynchus mykiss) nasal epithelium. Nasal CD8α+ cells display a distinct phenotype suggestive of CD8+ T cells with high integrin β2 expression. Importantly, nasal CD8α+ cells are located in clusters at the mucosal tip of each olfactory lamella but scattered in the neuroepithelial region. The grouping of CD8α+ cells may be explained by the greater expression of CCL19, ICAM-1, and VCAM-1 in the mucosal tip compared with the neuroepithelium. Whereas viral Ag uptake occurred via both tip and lateral routes, tip-resident MHC class II+ cells are located significantly closer to the lumen of the nasal cavity than are their neuroepithelial counterparts, therefore having quicker access to invading pathogens. Our studies reveal compartmentalized mucosal immune responses within the nasal mucosa of a vertebrate species, a strategy that likely optimizes local immune responses while protecting olfactory sensory functions.
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Affiliation(s)
- Ali Sepahi
- Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM 87131
| | - Elisa Casadei
- Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM 87131
| | - Luca Tacchi
- Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM 87131
| | - Pilar Muñoz
- Departamento de Sanidad Animal, Facultad de Veterinaria, Campus de Excelencia Internacional Regional Campus Mare Nostrum, Universidad de Murcia, 30100 Murcia, Spain; and
| | | | - Irene Salinas
- Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM 87131;
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Caradonna L, Amati L, Magrone T, Pellegrino N, Jirillo E, Caccavo D. Invited review: Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/09680519000060030101] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) [inflammatory bowel disease (IBD)] are both characterized by an exaggerated immune response at the gut associated lymphoreticular tissue level. Such an abnormal and dysregulated immune response may be directed against luminal and/or enteric bacterial antigens, as also supported by murine models of inflammatory bowel disease (IBD) caused by organisms such as Citrobacter rodentium and Helicobacter hepaticus. Bacterial endotoxins or lipopolysaccharides (LPS) have been detected in the plasma of IBD patients and an abnormal microflora and/or an increased permeability of the intestinal mucosa have been invoked as cofactors responsible for endotoxemia. At the same time, the evidence that phagocytosis and killing exerted by polymorphonuclear cells and monocytes and the T-cell dependent antibacterial activity are decreased in IBD patients may also explain the origin of LPS in these diseases. In IBD, pro-inflammatory cytokines and chemokines have been detected in elevated amounts in mucosal tissue and/or in peripheral blood, thus suggesting a monocyte/macrophage stimulation by enteric bacteria and/or their constituents ( e.g. LPS). On these grounds, in experimental models and in human IBD, anti-cytokine monoclonal antibodies and interleukin receptor antagonists are under investigation for their capacity to neutralize the noxious effects of immune mediators. Finally, the administration of lactobacilli is beneficial in human IBD and, in murine colitis, this treatment leads to a normalization of intestinal flora, reducing the number of colonic mucosal adherent and translocated bacteria.
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Affiliation(s)
- L. Caradonna
- Scientific Institute for Gastrointestinal Diseases, Castellana Grotte, Bari, Italy
| | - L. Amati
- Scientific Institute for Gastrointestinal Diseases, Castellana Grotte, Bari, Italy
| | - T. Magrone
- Scientific Institute for Gastrointestinal Diseases, Castellana Grotte, Bari, Italy
| | - N.M. Pellegrino
- Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy
| | - E. Jirillo
- Scientific Institute for Gastrointestinal Diseases, Castellana Grotte, Bari, Italy, Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy,
| | - D. Caccavo
- Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy
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36
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Benjelloun F, Oruc Z, Thielens N, Verrier B, Champier G, Vincent N, Rochereau N, Girard A, Jospin F, Chanut B, Genin C, Cogné M, Paul S. First Membrane Proximal External Region–Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations. THE JOURNAL OF IMMUNOLOGY 2016; 197:1979-88. [DOI: 10.4049/jimmunol.1600309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 07/03/2016] [Indexed: 11/19/2022]
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37
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Marinova S, Nenkov P, Markova R, Nikolaeva S, Kostadinova R, Mitov I, Vretenarska M. Cellular and Humoral Systemic and Mucosal Immune Responses Stimulated by an Oral Polybacterial Immunomodulator in Patients with Chronic Urinary Tract Infections. Int J Immunopathol Pharmacol 2016; 18:457-473. [PMID: 16164822 DOI: 10.1177/039463200501800306] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
An oral polybacterial immunomodulator Urostim (U), composed of killed cells and their lysates from E. coli expressing type 1 and P-pili, E. coli Re mutant, P. mirabilis, K. pneumoniae and E. faecalis was created for immunoprophylaxis and immunotherapy of urinary tract infections (UTIs). In experimental animal models, the stimulating effect of U on lymphocyte functional activity, macrophage phagocytosis and antibody producing cells, was established. In this study the immuno-modulating effects of U on the proliferating capacity and ultrastructural morphologic changes of lymphocytes, cytokine production and specific systemic humoral and mucosal immune responses in patients with UTIs have been evaluated. Patients enrolled in the study, received orally 50 mg U daily for a period of three months. On days 0,30 and 90 a quantitative analysis was performed on lymphoproliferative responses to polyclonal mitogens, IL-2 and the specific antigen U, the production of specific serum and saliva IgA, IgM and IgG antibodies to all components of U and the concentration of pro-inflammatory cytokines. There was significant improvement of non-specific and specific lymphoproliferative responses on days 30 and 90 after the onset of treatment with U, confirmed by electron-microscopic studies. The highest concentrations of serum proinflammatory cytokines TNF-α, IL-1β, and IL-6 were registered at baseline followed by a decrease until the end of the observation period. This finding correlates with the gradual decrease of immune activation as measured by the spontaneous lymphocyte proliferation. Data from the production of specific antibacterial antibodies in serum and saliva show two types of reactions. The first type was registered in patients with low pre-treatment levels in whom the concentration of specific antibodies increased on days 30 and 90. The second type of reaction was observed in patients with high pre-treatment levels, which dropped on day 30 and were usually followed by an increase at the end of the study. These results provide evidence for the immuno-modulating effect of U. Our data show that the oral administration of the polybacterial immunomodulator Urostim stimulates adequate cellular and humoral systemic and mucosal immune responses in patients with chronic UTIs.
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Affiliation(s)
- S Marinova
- National Center of Infectious and Parasitic Diseases (NCIPD), Sofia, Bulgaria
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38
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de Moreno de LeBlanc A, Galdeano CM, Chaves S, Perdigón G. Oral Administration of L. Casei CRL 431 Increases Immunity in Bronchus and Mammary Glands. EUR J INFLAMM 2016. [DOI: 10.1177/1721727x0500300105] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Lactic acid bacteria (LAB) found in numerous fermented products can interact with the gut associated lymphoid tissue increasing antibody (principally secretory IgA) production. IgA secreting cells can repopulate not only the lamina propria but also they can go to other distant sites such as bronchus, urogenital tract and mammary glands a phenomenon known as the IgA cycle. Later studies have shown that both B cells of other isotypes and T cells from Peyer's patches also exhibit gut-seeking properties. The aim of this study was to study the effect of different feeding periods of L. casei CRL 431 on the interaction with the immune cells in Peyer's patches studying the migration of not only the IgA+ cells, but also other immune cells (T lymphocytes) to other mucosal sites such as bronchus and mammary glands. BALB/c mice were fed with L. casei CRL 431 during 2, 5 or 7 days. At the end of the feeding period, the mice were killed and the small intestine, the lung and the mammary glands were removed. IgA+ cells and CD4+ and CD8+ T lymphocytes were counted in tissue slices using direct immunofluorescence. IgA+ cells increased in the intestine samples taken after 7 days of LAB feeding. In mammary gland and lung tissues, IgA+ cells increased after five days of feeding. CD4+ and CD8+ T lymphocytes were not able to migrate to sites distant from the intestine and their number did not increase in the lamina propria of the small intestine. L. casei CRL 431 was able to stimulate the IgA cycle without proliferation of T population. These results allow us to suggest that this LAB could be used as oral adjuvant to protect mucosal surfaces from intestinal and respiratory diseases, and would also be useful as an adjuvant to protect against mammary glands pathologies such as cancer.
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Affiliation(s)
- A. de Moreno de LeBlanc
- Centro de Referencia para lactobacilos (CERELA). Chacabuco 145, (4000) Tucumán. Argentina
- Cátedra de Inmunologia. Instituto de Microbiología. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán, Argentina
| | - C. Maldonado Galdeano
- Centro de Referencia para lactobacilos (CERELA). Chacabuco 145, (4000) Tucumán. Argentina
- Cátedra de Inmunologia. Instituto de Microbiología. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán, Argentina
| | - S. Chaves
- Centro de Referencia para lactobacilos (CERELA). Chacabuco 145, (4000) Tucumán. Argentina
| | - G. Perdigón
- Centro de Referencia para lactobacilos (CERELA). Chacabuco 145, (4000) Tucumán. Argentina
- Cátedra de Inmunologia. Instituto de Microbiología. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán, Argentina
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Orysiak J, Malczewska-Lenczowska J, Bik-Multanowski M. Expression of SCGB1C1 gene as a potential marker of susceptibility to upper respiratory tract infections in elite athletes - a pilot study. Biol Sport 2016; 33:107-10. [PMID: 27274102 PMCID: PMC4885620 DOI: 10.5604/20831862.1196510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 11/30/2015] [Accepted: 02/27/2016] [Indexed: 11/18/2022] Open
Abstract
High levels of exercise in athletes result in temporary immunosuppression, which could increase the susceptibility to upper respiratory tract infections. Understanding of immunological mechanisms responsible for this phenomenon could enable optimization of training schemes for elite athletes and avoidance of infection-related episodes of absence during sports championships. The aim of this study was to detect genes that may be responsible for modulation of individual susceptibility to infections. The blood and saliva samples were collected from 10 healthy, medically examined kayakers (4 females and 6 males) aged 24.7 ± 2.3 years. All samples were taken in the morning, after overnight fasting, in a seated position. The ELISA method was used to determine the levels of secretory immunoglobulin A (sIgA) and interleukin 5 (IL-5). Whole genome expression in blood was assessed using microarrays. The study did not reveal any significant correlation between genome expression and sIgA concentration. However, low expression of a gene involved in protection against the common cold – secretoglobin 1C1 (SCGB1C1) – was detected in athletes with high IL-5 concentrations (corrected p = 0.00065; fold change = 3.17). Our results suggest that blood expression of the SCGB1C1 gene might be a marker of susceptibility to upper respiratory tract infections in athletes.
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Affiliation(s)
- J Orysiak
- Department of Nutrition Physiology, Institute of Sport - National Research Institute, Warsaw, Poland
| | - J Malczewska-Lenczowska
- Department of Nutrition Physiology, Institute of Sport - National Research Institute, Warsaw, Poland
| | - M Bik-Multanowski
- Department of Medical Genetics, Jagiellonian University Medical College, Krakow, Poland
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40
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Guzman-Bautista ER, Ramirez-Estudillo MC, Rojas-Gomez OI, Vega-Lopez MA. Tracheal and bronchial polymeric immunoglobulin secretory immune system (PISIS) development in a porcine model. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2015; 53:271-282. [PMID: 26188097 DOI: 10.1016/j.dci.2015.07.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 07/11/2015] [Accepted: 07/14/2015] [Indexed: 06/04/2023]
Abstract
Polymeric immunoglobulins (pIgs) mucosal secretion is mediated by the pIg secretory immune system (PISIS), which is composed of J-chain (JC) and antibody (IgM/IgA) producing cells (JC-AbPC), pIg receptor (pIgR) epithelial cell expression and the efficient release of secretory Igs (SIgs) to the mucosal lumen. A poor development or disturbances in this system may cause higher infection susceptibility, as observed in young and elderly people. In spite of this system's importance, few detailed studies regarding its development have been described in the lower respiratory tract of humans. Because the porcine model has been reported as an option for translational medicine to humans, we studied the tracheal and bronchial PISIS development in healthy, non-vaccinated, SPF, miniature Vietnamese pigs from birth to adulthood using immunohistochemistry and ELISAs. Our results demonstrated that pIgR was present at birth, and its expression increased with age. In contrast, JC-AbPC were low in neonatal pigs; however, colostrum was a source of IgM, SIgA, total IgA and IgG in respiratory secretions (trachea and bronchoalveolar lavages, nasal secretion and saliva) in piglets. JC-AbPC steadily increased in post-weaned, young and adult pigs, correlating with considerable increases in secretory and total Igs in the trachea and bronchi. These data suggest a compensatory role of maternal Igs at the respiratory mucosa in the absence of a structured PISIS before weaning. Furthermore, monomeric Igs (IgG and IgA) may also play an important role in respiratory protection and deserves a more thorough study.
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Affiliation(s)
- E R Guzman-Bautista
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Laboratorio de Inmunobiología de las Mucosas, Avenida Instituto Politécnico Nacional # 2508, Colonia San Pedro Zacatenco, México 07360, D.F., Mexico
| | - M C Ramirez-Estudillo
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Laboratorio de Inmunobiología de las Mucosas, Avenida Instituto Politécnico Nacional # 2508, Colonia San Pedro Zacatenco, México 07360, D.F., Mexico
| | - O I Rojas-Gomez
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Laboratorio de Inmunobiología de las Mucosas, Avenida Instituto Politécnico Nacional # 2508, Colonia San Pedro Zacatenco, México 07360, D.F., Mexico
| | - M A Vega-Lopez
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Laboratorio de Inmunobiología de las Mucosas, Avenida Instituto Politécnico Nacional # 2508, Colonia San Pedro Zacatenco, México 07360, D.F., Mexico.
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41
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Kapoor K, Singh O. Ileal and jejunal Peyer's patches in buffalo calves: Histomorphological comparison. Vet World 2015; 8:1273-8. [PMID: 27047029 PMCID: PMC4774737 DOI: 10.14202/vetworld.2015.1273-1278] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/20/2015] [Accepted: 09/23/2015] [Indexed: 11/25/2022] Open
Abstract
Aim: The present study was aimed to elucidate the histomorphology of ileal and jejunal Peyer’s patches in the small intestine of buffalo calves and their structural comparison. Materials and Methods: The study was conducted on neonatal (n=10) and pre-pubertal (n=10) buffalo calves. The age of the postnatal buffalo calves was estimated by their temporary and permanent dentition. Results: The study revealed that several layers of oval to elongate elliptical lymphoid follicles were observed in submucosa on the anti-mesenteric side in the ileum of early neonatal calves. However, the follicles at this age, in jejunum were of all shapes present within one layer. The interfollicular space was occupied by the interfollicular tissue, which was diffuse and wider around jejunal lymphoid follicles as compared to ileal lymphoid follicles. However, toward the pubertal stage, the number of layers of lymphoid follicles was reduced in ileum due to involution while it remained similar in number in jejunum at this stage. Conclusion: The ileal Peyer’s patches were found to have started involution more or less around reaching puberty, whereas the jejunal Peyer’s patches appear to be functional throughout the lifespan of the animal.
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Affiliation(s)
- Kritima Kapoor
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
| | - Opinder Singh
- Department of Veterinary Anatomy, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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42
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Pedrotti LP, Barrios BE, Maccio-Maretto L, Bento AF, Sena AA, Rodriguez-Galán MC, Calixto JB, Correa SG. Systemic IL-12 burst expands intestinal T-lymphocyte subsets bearing the α₄ β₇ integrin in mice. Eur J Immunol 2015; 46:70-80. [PMID: 26464149 DOI: 10.1002/eji.201545585] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 09/11/2015] [Accepted: 10/06/2015] [Indexed: 12/25/2022]
Abstract
The intestinal immune system is complex and displays unique anatomic and functional characteristics. Numerous immune cell subsets are located beneath the epithelial barrier and their activity is highly regulated. Using hydrodynamic shear of IL-12 cDNA to achieve systemic expression of IL-12 in mice, we evaluated the effect of a transient burst of this cytokine on the activation status of T cells from Peyer's patches (PPs), mesenteric lymph nodes (MLNs), and colonic lamina propria (LP). Following systemic IL-12 release, intestinal T lymphocytes became activated, exhibiting a CD44(high) CD62L(-) phenotype. After 5 days of the cytokine burst, the frequency of α4β7(+) CD4(+) and CD8(+) cells increased, and CD8(+) α4β7(+) cells mainly expressed T bet, a critical regulator of the Th1 differentiation program. The incremental increase in α4β7 expression involved the IL-12 receptor-signal transducer and activator of transcription (STAT)-4 axis, and occurred independently of IFN-γ, IL-4, IL-10, and TNF-α signaling. Moreover, IL-12 priming exacerbated the outcome of acute dextran sodium sulphate (DSS)-induced colitis with higher scores of weight loss, blood in stool, and diarrhea and lower hematocrit. Together, our findings demonstrate that systemic polarizing signals could effectively expand the number of effector cells able to home to the LP and contribute to local inflammation.
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Affiliation(s)
- Luciano P Pedrotti
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
| | - Bibiana E Barrios
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
| | - Lisa Maccio-Maretto
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
| | - Allisson F Bento
- Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brasil
| | - Angela A Sena
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
| | - María Cecilia Rodriguez-Galán
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
| | - João B Calixto
- Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brasil
| | - Silvia G Correa
- Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina
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43
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Hernandez MO, Mantis NJ. Phenotypic Analysis of a Population of IgA+ Cells in the Follicle-Associated Epithelium of Mouse Peyer's Patches. PLoS One 2015; 10:e0124111. [PMID: 25894545 PMCID: PMC4404297 DOI: 10.1371/journal.pone.0124111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 02/25/2015] [Indexed: 01/12/2023] Open
Abstract
The follicle-associated epithelium (FAE) selectively transports prions, viruses, pathogenic bacteria, commensal microflora, and even secretory IgA (SIgA)-immune complexes from the intestinal lumen to underlying gut-associated lymphoid tissues like Peyer’s patches. The FAE consists of a single layer of columnar epithelial cells that includes enterocytes and M (microfold) cells, intermingled with dendritic cells (DCs), macrophages, and naïve and memory B and T lymphocytes. In this report we describe a population of IgA+ cells that reside within and immediately below the FAE in mouse Peyer’s patches. Immunofluorescence microscopy analysis indicated that the FAE-associated IgA+ cells were negative for surface antigen markers specific for B cells (B220), T cells (CD3), DCs (CD11c), and plasma cells (CD138). The IgA+ cells were also negative Ki-67 and IRF4, indicating that they are not mature B cells or plasma cells. The IgA+ cells were, however, often found in close proximity to DCs, leading us to speculate that the population of IgA+ cells in the FAE constitutes an atypical subset of B cells involved in mucosal antigen surveillance and/or immune recall.
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Affiliation(s)
- Maria Olga Hernandez
- Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, 12208, United States of America
| | - Nicholas J. Mantis
- Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, 12208, United States of America
- Department of Biomedical Sciences, University at Albany, Albany, New York, 12208, United States of America
- * E-mail:
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44
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Pei R, Martin DA, DiMarco DM, Bolling BW. Evidence for the effects of yogurt on gut health and obesity. Crit Rev Food Sci Nutr 2015; 57:1569-1583. [DOI: 10.1080/10408398.2014.883356] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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45
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Kikuchi Y, Yoshida H, Ogita T, Okita K, Fukudome SI, Suzuki T, Tanabe S. In vivo dose response and in vitro mechanistic analysis of enhanced immunoglobulin A production by Lactobacillus plantarum AYA. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2015. [PMID: 26221576 PMCID: PMC4513256 DOI: 10.12938/bmfh.2014-016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Secretory immunoglobulin A (IgA) mediates the mucosal immune system, which provides the first line of defense against inhaled and ingested pathogenic bacteria and viruses. Lactobacillus plantarum AYA increases the IgA level of Peyer’s patch (PP) cells, but the recommended amount of consumption and the mechanism of action remains unclear. Better understanding of these is essential to development of L. plantarum AYA for use in functional foods. Therefore, we investigated the dose-response effect (in vivo) and mechanism (in vitro) of IgA enhancement induced by L. plantarum AYA. In the small intestine of the mice fed a diet containing 0.03% or 0.3% of L. plantarum AYA powder for 4 weeks, the IgA levels were significantly increased. Thus, it is suggested that the recommended amount of consumption of L. plantarum AYA is about 0.72 mg per day. In addition, the
bacterial cell wall fraction significantly enhanced the IgA production level of murine PP cells in the in vitro assay. The ability of whole cells and the cell wall fraction to enhance IgA levels was significantly inhibited by an anti-Toll-like receptor-2 (TLR-2) antibody, which suggests that the cell wall fraction of L. plantarum AYA increases the IgA level via TLR-2. These findings indicate that L. plantarum AYA is a potential functional food source that maintains mucosal immunity.
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Affiliation(s)
- Yosuke Kikuchi
- Research Center for Basic Science, Research, and Development, Quality Assurance Division, Nisshin Seifun Group Inc., 5-3-1 Tsurugaoka, Fujimino, Saitama 356-8511, Japan
| | - Hikaru Yoshida
- Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8528, Japan
| | - Tasuku Ogita
- Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8528, Japan
| | - Kimiko Okita
- Yeast Function Development Unit, Oriental Yeast Co., Ltd., 3-6-10 Azusawa, Itabashi, Tokyo 174-8505, Japan
| | - Shin-Ichi Fukudome
- Research Center for Basic Science, Research, and Development, Quality Assurance Division, Nisshin Seifun Group Inc., 5-3-1 Tsurugaoka, Fujimino, Saitama 356-8511, Japan
| | - Takuya Suzuki
- Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8528, Japan
| | - Soichi Tanabe
- Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8528, Japan
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46
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Zheng R, Li X, Cao B, Zuo T, Wu J, Wang J, Xue C, Tang Q. Dietary Apostichopus japonicus enhances the respiratory and intestinal mucosal immunity in immunosuppressive mice. Biosci Biotechnol Biochem 2015; 79:253-9. [DOI: 10.1080/09168451.2014.955454] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Abstract
Although Apostichopus japonicus is recognized as a food and drug resource with significant immunomodulatory activity, its role in regulating the mucosal immunity remains unclear. This study aimed to explore the effects of dietary A. japonicus on mucosal immunity with an immunosuppressive mouse model. The expression of lysozyme, secretory immunoglobulin A(sIgA), and immunoglobulin A(IgA) as well as polymeric immunoglobulin receptor(pIgR) in respiratory and intestine organs was investigated. The results showed that A. japonicus could improve both the systematic and mucosal immunity. The expression of lysozyme, sIgA, and IgA in the respiratory organ was increased more significantly. Consumption of A. japonicus with the dose of 512 mg kg−1, which equals to 1/2 sea cucumber per day for adults, showed better effects. This study elucidated positive effects of A. japonicus on mucosal immunity for the first time, suggesting that moderate consumption of A. japonicus is helpful in improving mucosal immunity and preventing exogenous infection.
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Affiliation(s)
- Rong Zheng
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Xuemin Li
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Binbin Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Tao Zuo
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Juan Wu
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Jingfeng Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
| | - Qingjuan Tang
- College of Food Science and Engineering, Ocean University of China, Qingdao, P.R. China
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47
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Kato LM, Kawamoto S, Maruya M, Fagarasan S. The role of the adaptive immune system in regulation of gut microbiota. Immunol Rev 2015; 260:67-75. [PMID: 24942682 DOI: 10.1111/imr.12185] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gut microbiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gut microbiota. The fitness of host immune system is reflected in the gut microbiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gut microbiota required for immune homeostasis.
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Affiliation(s)
- Lucia M Kato
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, Yokohama, Japan
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Laffleur B, Denis-Lagache N, Péron S, Sirac C, Moreau J, Cogné M. AID-induced remodeling of immunoglobulin genes and B cell fate. Oncotarget 2015; 5:1118-31. [PMID: 24851241 PMCID: PMC4012742 DOI: 10.18632/oncotarget.1546] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Survival and phenotype of normal and malignant B lymphocytes are critically dependent on constitutive signals by the B cell receptor (BCR) for antigen. In addition, either antigen ligation of the BCR or various mitogenic stimuli result in B cell activation and induction of activation-induced deaminase (AID). AID activity can in turn mediate somatic hypermutation (SHM) of immunoglobulin (Ig) V regions and also deeply remodel the Ig heavy chain locus through class switch recombination (CSR) or locus suicide recombination (LSR). In addition to changes linked to affinity for antigen, modifying the class/isotype (i.e. the structure and function) of the BCR or suddenly deleting BCR expression also modulates the fate of antigen-experienced B cells.
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49
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Rai B, Kaur J, Foing BH. Wound healing and mucosal immunity during short Mars analog environment mission: salivary biomarkers and its clinical implications. Eurasian J Med 2015; 44:63-7. [PMID: 25610211 DOI: 10.5152/eajm.2012.16] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 02/27/2012] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE Wound healing in an extreme environment with micro-gravity is not well characterized, despite the likelihood that the increasing use of manned spaceflight as a research and commercial enterprise raises the probability of traumatic injury in this state. Hence, this study was conducted to determine the impact of the isolated environment of the Mars Desert Research Station on mucosal immunity and wound healing. MATERIALS AND METHODS Two punch biopsy wounds were placed on the hard palate of two crewmembers. The first wound was made during summer vacation, whereas the second was placed on the contra-lateral side 3 days before the Mars analog mission began. Thus, each crewmember served as his/her own control. Two independent methods were used to assess healing. A ten-item perceived stress scale, salivary cortisol, Immunoglobulin A, IgG and IgM were measured. RESULTS There were significant differences in the proportion of the wound size healed between vacation and the mission. Salivary IgA, IgM, IgG and cortisol levels showed significant differences between vacation and mission. CONCLUSION These data suggest that stress can have significant consequences for wound healing. The effects of stress on wound repair could have important clinical implications, including for recovery from surgery.
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Affiliation(s)
- Balwant Rai
- Earth&Life Sciences, Vrije Universiteit Amsterdam&ILEWG, Amsterdam, The Netherlands
| | - Jasdeep Kaur
- JBR Institute of Health Education Research and Technology, Punjab, India
| | - Bernard H Foing
- Earth&Life Sciences, Vrije Universiteit Amsterdam&ILEWG, Amsterdam, The Netherlands
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