肠道分节丝状菌（SFB）鞭毛蛋白FliC3影响宿主特异性黏附机制研究

宿主特异性黏附是肠道分节丝状菌SFB发挥免疫调控功能的前提条件。然而，SFB特异性黏附的分子机理并不清楚。本团队前期研究表明小鼠肠道内SFB表达鞭毛蛋白FliC3；小鼠SFB-FliC3比大鼠SFB-FliC3更稳定地结合小鼠回肠黏膜组织中黏附信号通路相关的蛋白；融合表达SFB-fliC3的乳酸乳球菌可以宿主特异性黏附在小鼠回肠末端黏膜上皮细胞。因此，我们推断SFB-FliC3参与SFB在肠道上皮细胞表面特异性黏附。本项目将分别采用细胞模型、SPF和无菌动物模型进一步验证SFB-FliC3的宿主特异性黏附功能；并通过iTRAQ定量蛋白组的方法筛选SFB-FliC3刺激引起的差异表达蛋白，找到应答SFB-FliC3的宿主效应蛋白与信号通路；最后，采用免疫共沉淀等方法对相互作用蛋白进行验证。本项目的实施将为深入研究SFB宿主特异性黏附的发生机理，以及进一步研究SFB免疫调控机制奠定基础。

Host specific adhesion is a precondition for immunoregulation of the intestine by segmented filamentous bacteria (SFB). However, the mechanism for SFB specific adhesion is not clear. Our previous research showed that expression of SFB flagellin FliC3 could be detected in mouse intestine. Additionally, mouse SFB-FliC3 tended to bind to adhesion-related proteins from the mouse ileum more stable than rat SFB-FliC3. We also found that SFB-fliC3-egfp-Lactococcus lactis can adhere to the mice ileal mucosa by the host specific way. Therefore, we hypothesize that SFB-FliC3 is involved in the adhesion of SFB to the surface of the intestinal epithelial cells, and this adhesion has a host specificity. This project will determine host specificity for the adhesion of SFB-FliC3 using comparing cell models, and animal models including specific-pathogen-free and germ-free mouse. Additionally, we will use iTRAQ method to identify host proteins and signaling pathways that respond to the expression of SFB-FliC3. These protein-protein interactions will be validated using in vitro immunoprecipitation methods. This project will lay the foundation for further research on the specific adhesion and immunoregulation mechanisms of SFB.