The role of Th17 cytokines in H.pylori infection

Th17细胞因子在幽门螺杆菌感染中的作用

• 批准号: 8398918
• 负责人: HOLLY Marie Scott ALGOOD
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8398918
• 关键词: A Mouse; Address; Afghanistan; B-Lymphocytes; Bacteria; Carcinogens; Cells; Chronic; Chronic Gastritis; Conflict (Psychology); Country; Data; Developing Countries; Disease; Epithelial Cells; Equilibrium; Far East; Gastric Adenocarcinoma; Gastric mucosa; Gastritis; Gram-Negative Bacteria; Growth; Health; Helicobacter Infections; Helicobacter pylori; Host Defense; Immune; Immune response; Immune system; Individual; Infection; Infection Control; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Interleukin-17; Iraq; Korea; Lead; Link; Location; Lymphocyte; Maintenance; Malignant Neoplasms; Mediating; Middle East; Modeling; Mus; Neutrophil Activation; Neutrophil Infiltration; Outcome; Pathology; Peptic Ulcer; Persons; Phenotype; Play; Population; Prevalence; Psoriasis; Receptor Signaling; Regulatory Pathway; Relative (related person); Rheumatoid Arthritis; Role; Signal Transduction; Site; Skin; Stomach; T cell response; T-Lymphocyte; Travel; United States; Vaccines; Veterans; Wild Type Mouse; World Health Organization; adverse outcome; antimicrobial; body system; cell motility; cell type; chemokine; cytokine; design; driving force; extracellular; granulocyte; immunopathology; in vivo; interest; interleukin-22; malignant stomach neoplasm; neutrophil; pathogen; public health relevance; receptor; research study; respiratory; response; tissue culture

DESCRIPTION (provided by applicant): The immune response to Helicobacter pylori is ineffective in clearing infection, but in most cases it successfully restricts bacterial proliferation, and most H. pylori-infected persons remain asymptomatic. A T helper 17 response to H. pylori is required for control of infection, but also controls inflammation and immune cell migration. Our own studies have identified IL-17 signaling as an essential regulator of the host response to H. pylori and a strong candidate for a link between T cell activity and effector functions. The mechanisms by which IL-17 regulates bacterial- host interactions are not completely understood. Addressing the role of T helper 17 cytokines, including IL-17A, IL-17F, and IL-22, during H. pylori infection is particularly interesting because H. pylori is a persistent infection which can lead to adverse outcomes including peptic ulcers and gastric cancer. It is well accepted that IL-17 induces chemokine expression in epithelial cells for the recruitment of neutrophils, but since the receptor for IL-17, IL-17RA, is expressed on many cell types, including epithelial cells, granulocytes, and lymphocytes, its effects are even more widespread. The specific aims are designed to elucidate the relative contributions of cytokines produced by Th17 cells to the epithelial cell and neutrophil response and specifically in control of H. pylori infection and gastritis. We will (1) investigate the role of IL-17 and IL-22 cytokines in stimulating gastric epithelial cell expression of antimicrobial products during H. pylori infection. Moreover, we will (2) determine the role of IL-22 in control of bacterial colonization and maintenance of barrier function during H. pylori infection, and (3) determine whether IL-17 has a direct effect on neutrophil activation during H. pylori infection. In addition to enhancing our understanding of H. pylori infection, these experiments will contribute to our understanding of the immune pathology associated with mucosal infections and immune- mediated diseases, such as psoriasis, inflammatory bowel disease, and rheumatoid arthritis.

描述（由申请人提供）： 对幽门螺杆菌的免疫反应无法有效清除感染，但在大多数情况下，它成功地限制了细菌增殖，并且大多数幽门螺杆菌感染者仍然没有症状。 T 辅助细胞 17 对幽门螺杆菌的反应是控制感染所必需的，但也控制炎症和免疫细胞迁移。我们自己的研究已确定 IL-17 信号传导是宿主对幽门螺杆菌反应的重要调节因子，也是 T 细胞活性和效应器功能之间联系的有力候选者。 IL-17 调节细菌-宿主相互作用的机制尚不完全清楚。探讨辅助 T 17 细胞因子（包括 IL-17A、IL-17F 和 IL-22）在幽门螺杆菌感染过程中的作用特别有趣，因为幽门螺杆菌是一种持续性感染，可能导致消化性溃疡和胃溃疡等不良后果。癌症。人们普遍认为，IL-17 诱导上皮细胞中趋化因子表达以招募中性粒细胞，但由于 IL-17 受体 IL-17RA 在许多细胞类型上表达，包括上皮细胞、粒细胞和淋巴细胞，因此其影响甚至更为广泛。具体目标旨在阐明 Th17 细胞产生的细胞因子对上皮细胞和中性粒细胞反应的相对贡献，特别是在控制幽门螺杆菌感染和胃炎方面。我们将 (1) 研究幽门螺杆菌感染期间 IL-17 和 IL-22 细胞因子在刺激胃上皮细胞抗菌产物表达中的作用。此外，我们将 (2) 确定幽门螺杆菌感染期间 IL-22 在控制细菌定植和维持屏障功能中的作用，以及 (3) 确定幽门螺杆菌感染期间 IL-17 是否对中性粒细胞活化有直接影响感染。除了增强我们对幽门螺杆菌感染的了解外，这些实验还将有助于我们了解与粘膜感染和免疫介导疾病（例如牛皮癣、炎症性肠病和类风湿性关节炎）相关的免疫病理学。