EPITHELIAL-LYMPHOID CROSSTALK VIA IL-1, DEFENSE AGAINST CITROBACTER RODENTIUM

通过 IL-1 进行上皮-淋巴串扰，防御啮齿类柠檬酸杆菌

• 批准号: 8360340
• 负责人: JISHU SHI
• 金额: $ 18.07万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360340
• 关键词: Adhesions; Bacterial Proteins; Cell Proliferation; Cells; Citrobacter rodentium; Clinical; Colon; Disease; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Funding; Gap Junctions; Grant; HT29 Cells; Health; Homeostasis; Host Defense; Hyperplasia; Immune; Immunoglobulins; Infection; Inflammatory; Interleukin-1; Interleukin-18; Intestines; Killer Cells; Liver; Lymphoid; Mucosal Immunity; Mus; National Center for Research Resources; Natural Immunity; Neutrophil Infiltration; Principal Investigator; Production; Proteins; Research; Research Infrastructure; Resources; Role; Signal Transduction; Source; Spleen; Tight Junctions; United States National Institutes of Health; antimicrobial peptide; cost; cytokine; macrophage; migration; protein expression; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this proposal is to determine the role of IL-1 receptor type I (IL-1R1) in host defense against Citrobacter rodentium infection. We hypothesize that IL-1R1-initiated signaling is essential for MyD88-dependent mucosal immunity against Citrobacter rodentium. Specific Aim One: Determine the role of IL-1R1 signaling in intestinal epithelial cell homeostasis in C. rodentium infection. We hypothesize that IL-1R signaling is essential for intestinal epithelial cell proliferation, functional integrity, and antimicrobial peptide/protein expression in C. rodentium infection. Using HT-29 and Mode-K cells, we will determine the effects of IL-1¿ on cell proliferation, migration, and adhesion, as well as the expression of antimicrobial peptides and proteins, proinflammatory cytokine, and molecules involved in gap junction and tight junction. In addition, we will compared the clinical signs, colonic hyperplasia, and intestinal mucosal integrity in WT, MyD88 KO, IL-1R1 KO, and IL-18 KO mice infected with C. rodentium. Specific Aim Two: Determine the role of IL-1R signaling in mucosal innate immunity in C. rodentium infection. We hypothesize that IL-1R signaling is required for the induction and recruitment of neutrophils and the production of inflammatory cytokines by epithelial and immune cells in C. rodentium infection. We will evaluate the colonic production of proinflammatory cytokines, intestinal infiltration of neutrophils and macrophages, epithelial antimicrobial peptides and proteins, bacterial burden in segments of colon, liver, and spleen, and intestinal immunoglobulin levels on WT, MyD88 KO, IL-1R1 KO, and IL-18 KO mice infected with C. rodentium.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 本提案的目的是确定 I 型 IL-1 受体 (IL-1R1) 在宿主防御啮齿类柠檬酸杆菌感染中的作用。我们假设 IL-1R1 启动的信号传导对于 MyD88 依赖性的针对柠檬酸杆菌的粘膜免疫至关重要。 具体目标一：确定 IL-1R1 信号传导在啮齿类柠檬酸杆菌感染的肠上皮细胞稳态中的作用。 我们假设 IL-1R 信号传导对于啮齿类弯曲杆菌感染中肠上皮细胞增殖、功能完整性和抗菌肽/蛋白表达至关重要。 使用 HT-29 和 Mode-K 细胞，我们将确定 IL-1¿ 对细胞增殖、迁移和粘附的影响，以及抗菌肽和蛋白质、促炎细胞因子以及参与间隙连接和紧密连接的分子的表达。 此外，我们还将比较感染啮齿类柠檬酸杆菌的 WT、MyD88 KO、IL-1R1 KO 和 IL-18 KO 小鼠的临床体征、结肠增生和肠粘膜完整性。 具体目标二：确定 IL-1R 信号在啮齿类梭菌感染的粘膜先天免疫中的作用。 我们假设，在啮齿类柠檬酸杆菌感染中，IL-1R 信号对于中性粒细胞的诱导和募集以及上皮细胞和免疫细胞产生炎性细胞因子是必需的。我们将评估 WT、MyD88 KO、IL-1R1 KO 和 IL-18 KO 小鼠的结肠促炎细胞因子的产生、中性粒细胞和巨噬细胞的肠道浸润、上皮抗菌肽和蛋白质、结肠、肝脏和脾脏部分的细菌负荷以及肠道免疫球蛋白水平 感染了啮齿类梭菌。