肠道外源性致病菌定植是ICU获得性感染的病理基础，目前尚无理想方法对肠道致病菌进行去定植。作者研究显示定植因子CFA/I能促进肠道对外源性致病菌去定植，但其机制尚未阐明。本项目采用激光共聚焦、基因沉默和敲除等方法研究CFA/I对肠黏膜黏附分子受体的阻断作用，对致病菌在肠道内分布和定植的影响，对肠道体液免疫激活以及黏液层、肠黏膜和固有层内免疫应答反应的作用。应用流式细胞仪分离无菌小鼠肠黏膜固有层内CD4+T细胞亚群(Th1、Th2、Th17、Treg)，观察CFA/I对T细胞分化与成熟的影响；通过依次沉默Toll样受体1-9研究CFA/I作用的靶点；沉默Th1、Th17的MyD88和TRIF，明确CFA/I激活体内炎症反应信号通路；探讨CFA/I对肠黏膜屏障和肠道微生态环境保护作用是否与CFA/I通过Th2、Treg调控炎症反应有关。为降低ICU获得性感染开拓新途径。

The pathological basis of ICU acquired infection is the colonization of exogenous conditional pathogen in the intestine, moreover there is no ideal way to decolonize the exogenous conditional pathogen in the intestine. It was observed that the exogenous conditional pathogen could be decolonized by colonization factor antigen I (CFA/I) in the intestine, however the mechanisms is still unknown.The effects of CFA/I on the adhesion receptor in intestinal epithelial cells, the distribution and colonization of exogenous pathogen in gut, the activation of CFA/I on the intestinal humoral immune system and the effect of CFA/I on inflammatory reaction in the mucus layer, mucosa and lamina propria will be detected using laser scanning confocal,gene silencing and gene knockout methods. CD4+T subsets(Th1、Th2、Th17、Treg) will be separated from intestinal lamina propria of germ-free mice by Flow cytometry to investigate the effects of CFA/I on differentiation and maturation of CD4+ T cell subsets. The binding receptor of CFA/I on CD4+ T cells will be analyzed by silencing the TLR1 to TLR9 gene. Furthermore, the MyD88 gene or TRIF gene in Th1 and Th17 cells will be silenced to confirm the inflammatory signal pathway of CFA/I. To explore if the protective effects of CFA/I on gut barrier and intestinal microecological environment is associated with inflammatory reaction modulated by CFA/I through Th2 and Treg. The project provides a new way to prevent the ICU acquired infection.