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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是确定IL-1受体I型(IL-1R1)在宿主防御轮状柠檬酸杆菌感染中的作用。我们推测，IL-1R1启动的信号转导对于依赖MyD88的黏膜免疫是必不可少的。 具体目的一：探讨IL-1R1信号在轮状芽胞杆菌感染中肠上皮细胞动态平衡中的作用。我们推测IL-1R信号对新月形体感染时肠上皮细胞的增殖、功能完整性和抗菌肽/蛋白的表达是必不可少的。利用HT-29和Model-K细胞，我们将确定IL-1对细胞增殖、迁移和黏附的影响，以及抗菌肽和蛋白、促炎细胞因子以及参与缝隙连接和紧密连接的分子的表达。此外，我们还将比较WT、MyD88 KO、IL-1R1KO和IL-18KO感染轮状芽孢杆菌的WT、MyD88 KO、IL-1R1KO和IL-18KO小鼠的临床体征、结肠增生和肠粘膜完整性。 特异性目的二：探讨IL-1R信号在轮状芽胞杆菌感染的黏膜天然免疫中的作用。我们推测IL-1R信号通路在嗜中性粒细胞的诱导和募集以及上皮性细胞和免疫细胞产生炎性细胞因子的过程中是必需的。我们将评估WT、MyD88 KO、IL-1R1KO和IL-18KO感染的WT、MyD88 KO、IL-1R1KO和IL-18KO小鼠结肠促炎细胞因子的产生、中性粒细胞和巨噬细胞的肠道渗透、上皮抗菌肽和蛋白、结肠、肝和脾部分的细菌负荷以及肠道免疫球蛋白水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.