Regulation of intestinal barrier by E. coli curli fibrils

描述（由申请人提供）：淀粉样蛋白是细菌生物膜的常见成分，由细菌门、厚壁菌门和变形菌门的成员产生。最近，我们发现curli，一种在肠道细菌生物膜中发现的淀粉样蛋白，通过toll样受体2 (TLR2)/TLR1复合物被先天免疫系统识别。1917年大肠杆菌尼塞尔（尼塞尔）是由军医阿尔弗雷德·尼塞尔博士从一名士兵的粪便中分离出来的。在第一次世界大战期间，一名士兵在一次严重的志贺氏菌爆发中没有出现腹泻，此后许多研究调查了这种有机体用于益生菌治疗的潜在用途

DESCRIPTION (provided by applicant): Amyloids, a common component of the biofilms of bacteria, are produced by the members of Bacteriodetes, Firmicutes and Proteobacteria. Recently, we have shown that curli, an amyloid found within the biofilms of enteric bacteria, is recognized by the innate immune system through Toll-like receptor 2 (TLR2)/TLR1 complex. E. coli Nissle 1917 (Nissle) was isolated by the army surgeon Dr. Alfred Nissle from the feces of a soldier who did not develop diarrhea during a severe Shigella outbreak during World War I. Since then many studies investigated the potential use of this organism for probiotic therapy in Inflammatory Bowel Diseases (IBD). Clinical trials have shown that treatment with EcN was as efficient as the standard medication in preventing the relapse of Ulcerativ Colitis (UC). Following studies have discovered that Nissle reinforces the intestinal epithelial barrier function. Furthermore, TLR2 activation by Nissle has been shown to have immunomodulatory effects in the gastrointestinal tract. Nonetheless, the mechanisms by which EcN induces the latter affects remain unknown. The objective of this application is to investigate the contribution of bacterial amyloids to host intesinal immune responses. We hypothesize that the detection of bacterial amyloids via TLR2 in the gastrointestinal tract enables epithelial cells to serve as sentinels for bacterial translocation fom the gut lumen and respond by augmenting the epithelial barrier. We will test this hypothesis by studying the immunomodulatory function of curli fibrils produced by the commensal organism Nissle.