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1
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Malik K, Kodgire P. Insights into the molecular mechanisms of H. pylori-associated B-cell lymphoma. Crit Rev Microbiol 2024; 50:879-895. [PMID: 38288575 DOI: 10.1080/1040841x.2024.2305439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 12/13/2023] [Accepted: 01/06/2024] [Indexed: 10/09/2024]
Abstract
Cancer research has extensively explored various factors contributing to cancer development, including chemicals, drugs, smoking, and obesity. However, the role of bacterial infections in cancer induction remains underexplored. In particular, the mechanisms underlying H. pylori-induced B-cell lymphoma, a potential consequence of bacterial infection, have received little attention. In recent years, there has been speculation about contagious agents causing persistent inflammation and encouraging B-lymphocyte transition along with lymphomagenesis. MALT lymphoma associated with chronic H. pylori infection, apart from two other central associated lymphomas - Burkitt's Lymphoma and DLBCL, is well studied. Owing to the increasing colonization of H. pylori in the host gut and its possible action in the development of B-cell lymphoma, this review aims to summarize the existing reports on different B-cell lymphomas' probable association with H. pylori infections; also emphasizing the function of the organism in lymphomagenesis; including its interaction with the host, pathogen and host-specific factors, and tumor microenvironment.
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Affiliation(s)
- Kritika Malik
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Prashant Kodgire
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
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2
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Reuter S, Raspe J, Taube C. Microbes little helpers and suppliers for therapeutic asthma approaches. Respir Res 2024; 25:29. [PMID: 38218816 PMCID: PMC10787474 DOI: 10.1186/s12931-023-02660-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/28/2023] [Indexed: 01/15/2024] Open
Abstract
Bronchial asthma is a prevalent and increasingly chronic inflammatory lung disease affecting over 300 million people globally. Initially considered an allergic disorder driven by mast cells and eosinophils, asthma is now recognized as a complex syndrome with various clinical phenotypes and immunological endotypes. These encompass type 2 inflammatory endotypes characterized by interleukin (IL)-4, IL-5, and IL-13 dominance, alongside others featuring mixed or non-eosinophilic inflammation. Therapeutic success varies significantly based on asthma phenotypes, with inhaled corticosteroids and beta-2 agonists effective for milder forms, but limited in severe cases. Novel antibody-based therapies have shown promise, primarily for severe allergic and type 2-high asthma. To address this gap, novel treatment strategies are essential for better control of asthma pathology, prevention, and exacerbation reduction. One promising approach involves stimulating endogenous anti-inflammatory responses through regulatory T cells (Tregs). Tregs play a vital role in maintaining immune homeostasis, preventing autoimmunity, and mitigating excessive inflammation after pathogenic encounters. Tregs have demonstrated their ability to control both type 2-high and type 2-low inflammation in murine models and dampen human cell-dependent allergic airway inflammation. Furthermore, microbes, typically associated with disease development, have shown immune-dampening properties that could be harnessed for therapeutic benefits. Both commensal microbiota and pathogenic microbes have demonstrated potential in bacterial-host interactions for therapeutic purposes. This review explores microbe-associated approaches as potential treatments for inflammatory diseases, shedding light on current and future therapeutics.
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Affiliation(s)
- Sebastian Reuter
- Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Tüschener Weg 40, 45239, Essen, Germany.
| | - Jonas Raspe
- Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Tüschener Weg 40, 45239, Essen, Germany
| | - Christian Taube
- Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Tüschener Weg 40, 45239, Essen, Germany
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3
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Marzhoseyni Z, Mousavi MJ, Ghotloo S. Helicobacter pylori antigens as immunomodulators of immune system. Helicobacter 2024; 29:e13058. [PMID: 38380545 DOI: 10.1111/hel.13058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 02/07/2024] [Accepted: 02/08/2024] [Indexed: 02/22/2024]
Abstract
Helicobacter pylori (H. pylori) is one of the most prevalent human pathogens and the leading cause of chronic infection in almost half of the population in the world (~59%). The bacterium is a major leading cause of chronic gastritis, gastric and duodenal ulcers, and two type of malignancies, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Despite the immune responses mounted by the host, the bacteria are not cleared from the body resulting in a chronic infection accompanied by a chronic inflammation. Herein, a review of the literature discussing H. pylori antigens modulating the immune responses is presented. The mechanisms that are involved in the modulation of innate immune response, include modulation of recognition by pattern recognition receptors (PRRs) such as modulation of recognition by toll like receptors (TLR)4 and TLR5, modulation of phagocytic function, and modulation of phagocytic killing mediated by reactive oxygen species (ROS) and nitric oxide (NO). On the other hands, H. pylori modulates acquired immune response by the induction of tolerogenic dendritic cells (DCs), modulation of apoptosis, induction of regulatory T cells, modulation of T helper (Th)1 response, and modulation of Th17 response.
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Affiliation(s)
- Zeynab Marzhoseyni
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Javad Mousavi
- Department of Hematology, Faculty of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Somayeh Ghotloo
- Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
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4
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Xie J, Van Hoecke L, Vandenbroucke RE. The Impact of Systemic Inflammation on Alzheimer's Disease Pathology. Front Immunol 2022; 12:796867. [PMID: 35069578 PMCID: PMC8770958 DOI: 10.3389/fimmu.2021.796867] [Citation(s) in RCA: 149] [Impact Index Per Article: 49.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022] Open
Abstract
Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which the therapeutic effect is not yet conclusively proven, only symptomatic medication that is effective for some AD patients is available. In order to be able to design more rational and effective treatments, our understanding of the mechanisms behind the pathogenesis and progression of AD urgently needs to be improved. Over the last years, it became increasingly clear that peripheral inflammation is one of the detrimental factors that can contribute to the disease. Here, we discuss the current understanding of how systemic and intestinal (referred to as the gut-brain axis) inflammatory processes may affect brain pathology, with a specific focus on AD. Moreover, we give a comprehensive overview of the different preclinical as well as clinical studies that link peripheral Inflammation to AD initiation and progression. Altogether, this review broadens our understanding of the mechanisms behind AD pathology and may help in the rational design of further research aiming to identify novel therapeutic targets.
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Affiliation(s)
- Junhua Xie
- VIB Center for Inflammation Research, VIB, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Lien Van Hoecke
- VIB Center for Inflammation Research, VIB, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Roosmarijn E Vandenbroucke
- VIB Center for Inflammation Research, VIB, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
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5
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Uhl B, Prochazka KT, Fechter K, Pansy K, Greinix HT, Neumeister P, Deutsch AJA. Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas. World J Gastrointest Oncol 2022; 14:153-162. [PMID: 35116108 PMCID: PMC8790412 DOI: 10.4251/wjgo.v14.i1.153] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/16/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.
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Affiliation(s)
- Barbara Uhl
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | | | - Karoline Fechter
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | - Katrin Pansy
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | | | - Peter Neumeister
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
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6
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Liu S, Lyu J, Li Q, Wu X, Yang Y, Huo G, Zhu Q, Guo M, Shen Y, Wang S, Fan C. Generation of a uniform thymic malignant lymphoma model with C57BL/6J p53 gene deficient mice. J Toxicol Pathol 2022; 35:25-36. [PMID: 35221493 PMCID: PMC8828615 DOI: 10.1293/tox.2021-0022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/17/2021] [Indexed: 12/12/2022] Open
Abstract
Lymphoma is the third most common cancer diagnosed in children, and T-cell lymphoma has
the worst prognosis based on clinical observations. To date, a lymphoma model with uniform
penetrance has not yet been developed. In this study, we generated a p53
deficient mouse model by targeting embryonic stem cells derived from a C57BL/6J mouse
strain. Homozygous p53 deficient mice exhibited a higher rate of
spontaneous tumorigenesis, with a high spontaneous occurrence rate (93.3%) of malignant
lymphoma. Because tumor models with high phenotypic consistency are currently needed, we
generated a lymphoma model by a single intraperitoneal injection of 37.5 or 75 mg/kg
N-methyl-N-nitrosourea to p53 deficient mice. Lymphoma and retinal
degeneration occurred in 100% of p53+/− mice administered with
higher concentrations of N-methyl-N-nitrosourea, a much greater response than those of
previously reported models. The main anatomic sites of lymphoma were the thymus, spleen,
bone marrow, and lymph nodes. Both induced and spontaneous lymphomas in the thymus and
spleen stained positive for CD3 antigen, and flow cytometry detected positive CD4 and/or
CD8 cells. Based on our observations and previous data, we hypothesize that mice with a B6
background are prone to lymphomagenesis.
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Affiliation(s)
- Susu Liu
- Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, No. 31 Huatuo Road, Beijing Daxing district, Beijing 102629, China
| | - Jianjun Lyu
- Department of Pathology, InnoStar Bio-tech Nantong Co., Ltd., Nantong 226133, China
| | - Qianqian Li
- National Centre for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China
| | - Xi Wu
- Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, No. 31 Huatuo Road, Beijing Daxing district, Beijing 102629, China
| | - Yanwei Yang
- National Centre for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China
| | - Guitao Huo
- National Centre for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China
| | - Qingfen Zhu
- Shandong Institute for Food and Drug Control, No. 2749, Xinluo Road, High-tech Zone, Jinan 250101, China
| | - Ming Guo
- Shandong Institute for Food and Drug Control, No. 2749, Xinluo Road, High-tech Zone, Jinan 250101, China
| | - Yuelei Shen
- Beijing Biocytogen Co. LTD, No. 88 Kechuang 6th Avenue Ludong Area Economic-Technological Development Area, Beijing 101111, China
| | - Sanlong Wang
- National Centre for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China
| | - Changfa Fan
- Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, No. 31 Huatuo Road, Beijing Daxing district, Beijing 102629, China
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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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8
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Ruan G, Huang A, Hu C, Xu N, Fan M, Zhang Z, Wang Y, Xing Y. CD4 + CD8αα + T cells in the gastric epithelium mediate chronic inflammation induced by Helicobacter felis. Microb Pathog 2021; 159:105151. [PMID: 34450200 DOI: 10.1016/j.micpath.2021.105151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/23/2021] [Accepted: 08/14/2021] [Indexed: 01/28/2023]
Abstract
CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cells, are reported to contribute to local immunosuppression. However, the presence of DP T cells in Helicobacter. pylori -induced gastritis and their relationship with disease prognosis has yet to be elucidated. In this study, a chronic gastritis model was established by infecting mice with Helicobacter felis. Gastric-infiltrating lymphocytes were isolated from these mice and analyzed by flow cytometry. The frequency of DP T cells in H. felis-induced gastritis mice was higher than that in uninfected mice. The gastric DP T cells were derived from lamina propria cells but were predominantly distributed in the gastric epithelial layer. These gastric DP T cells also exhibited anti-inflammatory functions, and they inhibited the maturation of dendritic cells and proliferation of CD4+ T lymphocytes in vitro. Elimination of DP T cells simultaneously resulted in severe gastritis and a reduction of H. felis load in vivo. Finally, vaccine mixed with different adjuvants was used to explore the relationship between vaccine efficacy and DP cells. Silk fibroin as the vaccine delivery system enhanced vaccine efficacy by reducing the number of DP T cells. This study demonstrated that DP T cells perform an immunosuppressive role in Helicobacter felis-induced gastritis, and consequently, DP T cells may affect disease prognosis and vaccine efficacy.
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Affiliation(s)
- Guojing Ruan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - An Huang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Chupeng Hu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Ningyin Xu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Menghui Fan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Zhenxing Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Yue Wang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
| | - Yingying Xing
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
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9
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Aydın EM, Demir TD, Seymen N, Said SS, Oktem-Okullu S, Tiftikci A, Cicek B, Tokat F, Tozun N, Ince U, Sezerman U, Sayi-Yazgan A. The crosstalk between H. pylori virulence factors and the PD1:PD-L1 immune checkpoint inhibitors in progression to gastric cancer. Immunol Lett 2021; 239:1-11. [PMID: 34363898 DOI: 10.1016/j.imlet.2021.06.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 06/14/2021] [Accepted: 06/16/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death -ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. METHODS A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors' (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. RESULTS The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. CONCLUSION Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.
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Affiliation(s)
- Elif Merve Aydın
- Department of Molecular Biology and Genetics, Istanbul Technical University, Maslak, Istanbul, 34469, Turkey
| | - Tevriz Dilan Demir
- Department of Molecular Biology and Genetics, Istanbul Technical University, Maslak, Istanbul, 34469, Turkey
| | - Nogayhan Seymen
- Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34684, Turkey
| | - Sawsan Sudqi Said
- Department of Molecular Biology and Genetics, Istanbul Technical University, Maslak, Istanbul, 34469, Turkey
| | - Sinem Oktem-Okullu
- Department of Medical Microbiology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34684, Turkey
| | - Arzu Tiftikci
- Department of Internal Medicine, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34457, Turkey
| | - Bahattin Cicek
- Department of Internal Medicine, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34457, Turkey
| | - Fatma Tokat
- Department of Pathology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752, Istanbul, Turkey
| | - Nurdan Tozun
- Department of Internal Medicine, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34457, Turkey
| | - Umit Ince
- Department of Pathology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752, Istanbul, Turkey
| | - Ugur Sezerman
- Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul, 34684, Turkey
| | - Ayca Sayi-Yazgan
- Department of Molecular Biology and Genetics, Istanbul Technical University, Maslak, Istanbul, 34469, Turkey.
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10
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Xiao F, Liu X, Guo SW. Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis. Front Immunol 2020; 11:610963. [PMID: 33381124 PMCID: PMC7767909 DOI: 10.3389/fimmu.2020.610963] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 11/13/2020] [Indexed: 12/18/2022] Open
Abstract
Endometriosis is a hormonal disease, as well as a chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there is a wanton lack of a bigger picture on how these cells are coordinated to work concertedly. Since endometriotic lesions experience cyclical bleeding, they are fundamentally wounds that undergo repeated tissue injury and repair (ReTIAR). In this study, we attempted to characterize the role of platelets and regulatory T cells (Tregs) in modulating the lesional immune microenvironment and its subsequent effects on lesional progression and fibrogenesis. Through two mouse experiments, we show that, by disrupting predominantly a type 2 immune response in lesional microenvironment, both platelets and Tregs depletion decelerated lesional progression and fibrogenesis, likely through the suppression of the TGF-β1/Smad3 and PDGFR-β/PI3K/Akt signaling pathways. In particular, platelet depletion resulted in significantly reduced lesional expression of thymic stromal lymphopoietin (TSLP), leading to reduced aggregation of macrophages and alternatively activated (M2) macrophages, and of Tregs, T helper 2 (Th2) and Th17 cells but increased aggregation of Th1 cells, in lesions, which, in turn, yields retarded fibrogenesis. Similarly, Tregs depletion resulted in suppression of platelet aggregation, and reduced aggregation of M2 macrophages, Th2 and Th17 cells but increased aggregation of Th1 cells, in lesions. Thus, both platelet and Tregs depletion decelerated lesional progression and fibrogenesis by disrupting predominantly a type 2 immunity in lesional microenvironment. Taken together, this suggests that both platelets and Tregs may induce a type 2 immunity in lesional microenvironment that is conducive to lesional progression and fibrogenesis.
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Affiliation(s)
- Fengyi Xiao
- Shanghai OB/GYN Hospital, Fudan University, Shanghai, China
| | - Xishi Liu
- Shanghai OB/GYN Hospital, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China
| | - Sun-Wei Guo
- Shanghai OB/GYN Hospital, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China
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11
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APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection. Sci Rep 2020; 10:14858. [PMID: 32908188 PMCID: PMC7481773 DOI: 10.1038/s41598-020-71792-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 08/03/2020] [Indexed: 12/17/2022] Open
Abstract
The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.
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The Role of Gastric Mucosal Immunity in Gastric Diseases. J Immunol Res 2020; 2020:7927054. [PMID: 32775468 PMCID: PMC7396052 DOI: 10.1155/2020/7927054] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/30/2020] [Indexed: 12/17/2022] Open
Abstract
Gastric mucosa plays its immune function through innate and adaptive immunity by recruiting immune cells and releasing corresponding cytokines, which have an inseparable relationship with gastric diseases. Whether infective gastric diseases caused by Helicobacter pylori, Epstein-Barr virus or other microbe, noninfective gastric diseases, or gastric cancer, gastric mucosal immunity plays an important role in the occurrence and development of the disease. Understanding the unique immune-related tissue structure of the gastric mucosa and its role in immune responses can help prevent gastric diseases or treat them through immunotherapy. In this review, we summarize the basic feature of gastric mucosal immunity and its relationship with gastric diseases to track the latest progress of gastric mucosal immunity, update relevant knowledge and provide theoretical reference for the prevention and treatment of gastric diseases based on the gastric mucosal immunity.
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González A, Casado J, Chueca E, Salillas S, Velázquez-Campoy A, Espinosa Angarica V, Bénejat L, Guignard J, Giese A, Sancho J, Lehours P, Lanas Á. Repurposing Dihydropyridines for Treatment of Helicobacter pylori Infection. Pharmaceutics 2019; 11:pharmaceutics11120681. [PMID: 31847484 PMCID: PMC6969910 DOI: 10.3390/pharmaceutics11120681] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 12/12/2019] [Accepted: 12/13/2019] [Indexed: 12/11/2022] Open
Abstract
Antibiotic resistance is a major cause of the increasing failures in the current eradication therapies against Helicobacter pylori. In this scenario, repurposing drugs could be a valuable strategy to fast-track novel antimicrobial agents. In the present study, we analyzed the inhibitory capability of 1,4-dihydropyridine (DHP) antihypertensive drugs on the essential function of the H. pylori response regulator HsrA and investigated both the in vitro antimicrobial activities and the in vivo efficacy of DHP treatments against H. pylori. Six different commercially available and highly prescribed DHP drugs-namely, Nifedipine, Nicardipine, Nisoldipine, Nimodipine, Nitrendipine, and Lercanidipine-noticeably inhibited the DNA binding activity of HsrA and exhibited potent bactericidal activities against both metronidazole- and clarithromycin-resistant strains of H. pylori, with minimal inhibitory concentration (MIC) values in the range of 4 to 32 mg/L. The dynamics of the decline in the bacterial counts at 2 × MIC appeared to be correlated with the lipophilicity of the drugs, suggesting different translocation efficiencies of DHPs across the bacterial membrane. Oral treatments with 100 mg/kg/day of marketed formulations of Nimodipine or Nitrendipine in combination with omeprazole significantly reduced the H. pylori gastric colonization in mice. The results presented here support a novel therapeutic solution for treatment of antibiotic-resistant H. pylori infections.
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Affiliation(s)
- Andrés González
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Correspondence: ; Tel.: +34-976-762807
| | - Javier Casado
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Eduardo Chueca
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Sandra Salillas
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Adrián Velázquez-Campoy
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
- ARAID Foundation, Government of Aragon, Ranillas 1-D, 50018 Zaragoza, Spain
| | - Vladimir Espinosa Angarica
- Cancer Science Institute, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore
| | - Lucie Bénejat
- UMR1053 Bordeaux Research in Translational Oncology, INSERM, Université Bordeaux, BaRITOn, 33000 Bordeaux, France
- French National Reference Center for Campylobacters & Helicobacters, 33000 Bordeaux, France
| | - Jérome Guignard
- UMR1053 Bordeaux Research in Translational Oncology, INSERM, Université Bordeaux, BaRITOn, 33000 Bordeaux, France
| | - Alban Giese
- UMR1053 Bordeaux Research in Translational Oncology, INSERM, Université Bordeaux, BaRITOn, 33000 Bordeaux, France
| | - Javier Sancho
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquilor (Edif. I+D), 50018 Zaragoza, Spain
- Department of Biochemistry and Molecular & Cellular Biology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Philippe Lehours
- UMR1053 Bordeaux Research in Translational Oncology, INSERM, Université Bordeaux, BaRITOn, 33000 Bordeaux, France
- French National Reference Center for Campylobacters & Helicobacters, 33000 Bordeaux, France
| | - Ángel Lanas
- Aragon Institute for Health Research (IIS Aragón), San Juan Bosco 13, 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain
- Digestive Diseases Service, University Clinic Hospital Lozano Blesa; San Juan Bosco 15, 50009 Zaragoza, Spain
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
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Tseng CH. Metformin is associated with a lower risk of non-Hodgkin lymphoma in patients with type 2 diabetes. DIABETES & METABOLISM 2019; 45:458-464. [PMID: 31129317 DOI: 10.1016/j.diabet.2019.05.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Revised: 05/12/2019] [Accepted: 05/19/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Whether metformin use might affect the risk of non-Hodgkin lymphoma (NHL) remained to be answered. METHODS A total of 610,089 newly diagnosed type 2 diabetes patients with 2 or more times of prescription of antidiabetic drugs during 1999-2009 were enrolled from Taiwan's National Health Insurance database. They were followed up for NHL incidence until December 31, 2011. Both intention-to-treat and per-protocol analyses were conducted. Cox regression incorporated with the inverse probability of treatment-weighting using propensity scores was used to estimate hazard ratios. RESULTS There were 414,783 metformin initiators and 195,306 non-metformin initiators within the initial 12-month of prescriptions of antidiabetic drugs. After a median follow-up of 5.07 years in metformin initiators and 6.78 years in non-metformin initiators, 1076 and 755 patients were diagnosed of new-onset NHL, respectively. The respective incidence was 47.74 and 57.68 per 100,000 person-years and the hazard ratio for metformin initiators versus non-metformin initiators was 0.849 (95% confidence interval 0.773-0.932) in the intention-to-treat analysis. In the per-protocol analysis, the hazard ratio was 0.706 (95% confidence interval 0.616-0.808). Sensitivity analyses after excluding patients with irregular follow-up, with an extension of minimal observation periods of 24 or 36 months, with incretin-based therapies, or in patients enrolled during 2 different periods (i.e., 1999-2003 and 2004-2009) consistently showed a lower risk among metformin initiators in both the intention-to-treat and the per-protocol analyses. CONCLUSIONS Metformin use is associated with a lower risk of NHL compared with non-metformin antidiabetics.
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Affiliation(s)
- C-H Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan.
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Yang Y, Chen L, Sun HW, Guo H, Song Z, You Y, Yang LY, Tong YN, Gao JN, Zeng H, Yang WC, Zou QM. Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori. J Nanobiotechnology 2019; 17:6. [PMID: 30660182 PMCID: PMC6339695 DOI: 10.1186/s12951-019-0441-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 01/03/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response. RESULTS In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG. CONCLUSION This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.
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Affiliation(s)
- Yun Yang
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Li Chen
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
- Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China
| | - Hong-wu Sun
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Hong Guo
- Department of Gastroenterology, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China
| | - Zhen Song
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Ying You
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Liu-yang Yang
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Ya-nan Tong
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Ji-ning Gao
- Institute of Combined Injury of PLA, College of Military Preventive Medicine, Third Military Medical University of Chinese PLA, Chongqing, China
| | - Hao Zeng
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
| | - Wu-chen Yang
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
- Department of Gastroenterology, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China
- Department of Hematology, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China
| | - Quan-ming Zou
- National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China
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Karkhah A, Ebrahimpour S, Rostamtabar M, Koppolu V, Darvish S, Vasigala VKR, Validi M, Nouri HR. Helicobacter pylori evasion strategies of the host innate and adaptive immune responses to survive and develop gastrointestinal diseases. Microbiol Res 2018; 218:49-57. [PMID: 30454658 DOI: 10.1016/j.micres.2018.09.011] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 09/09/2018] [Accepted: 09/28/2018] [Indexed: 02/08/2023]
Abstract
Helicobacter pylori (H. pylori) is a bacterial pathogen that resides in more than half of the human population and has co-evolved with humans for more than 58,000 years. This bacterium is orally transmitted during childhood and is a key cause of chronic gastritis, peptic ulcers and two malignant cancers including MALT (mucosa-associated lymphoid tissue) lymphoma and adenocarcinoma. Despite the strong innate and adaptive immune responses, H. pylori has a long-term survival in the gastric mucosa. In addition to the virulence factors, survival of H. pylori is strongly influenced by the ability of bacteria to escape, disrupt and manipulate the host immune system. This bacterium can escape from recognition by innate immune receptors via altering its surface molecules. Moreover, H. pylori subverts adaptive immune response by modulation of effector T cell. In this review, we discuss the immune-pathogenicity of H. pylori by focusing on its ability to manipulate the innate and acquired immune responses to increase its survival in the gastric mucosa, leading up to gastrointestinal disorders. We also highlight the mechanisms that resulted to the persistence of H. pylori in gastric mucosa.
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Affiliation(s)
- Ahmad Karkhah
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Soheil Ebrahimpour
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Rostamtabar
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Veerendra Koppolu
- Scientist Biopharmaceutical Development Medimmune Gaithersburg, MD, 20878 USA
| | - Sorena Darvish
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | | | - Majid Validi
- Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hamid Reza Nouri
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Yang WC, Sun HW, Sun HQ, Yuan HM, Li B, Li HB, Hu J, Yang Y, Zou QM, Guo H, Wu C, Chen L. Intranasal immunization with immunodominant epitope peptides derived from HpaA conjugated with CpG adjuvant protected mice against Helicobacter pylori infection. Vaccine 2018; 36:6301-6306. [DOI: 10.1016/j.vaccine.2018.09.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 06/15/2018] [Accepted: 09/01/2018] [Indexed: 01/07/2023]
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Lekic A, Brekalo Z, Kvesic A, Kovacevic M, Baricev-Novakovic Z, Sutic I, Bulog A, Sutic I, Pavisic V, Mrakovcic-Sutic I. Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis. Scand J Immunol 2017; 86:65-71. [PMID: 28500763 DOI: 10.1111/sji.12563] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 04/30/2017] [Indexed: 01/14/2023]
Abstract
Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.
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Affiliation(s)
- A Lekic
- Department of Basic Medical Sciences, Faculty of Health Studies, University of Rijeka, Rijeka, Croatia
| | - Z Brekalo
- Department of Surgery, University Hospital Mostar, Mostar, Bosnia and Herzegovina
| | - A Kvesic
- Department of Surgery, University Hospital Mostar, Mostar, Bosnia and Herzegovina
| | - M Kovacevic
- Department of Cardiovascular Surgery, Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - Z Baricev-Novakovic
- Department of Family Medicine, Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - I Sutic
- Department of Family Medicine, Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - A Bulog
- Department of Public Health, Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - I Sutic
- Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - V Pavisic
- Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia
| | - I Mrakovcic-Sutic
- Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia
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Floch P, Izotte J, Guillemaud J, Sifré E, Costet P, Rousseau B, Laur AM, Giese A, Korolik V, Mégraud F, Dubus P, Hahne M, Lehours P. A New Animal Model of Gastric Lymphomagenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:1473-1484. [DOI: 10.1016/j.ajpath.2017.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 02/27/2017] [Accepted: 03/09/2017] [Indexed: 12/29/2022]
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