2007年，R?berg等提出感染耐受(infection-tolerance)是宿主防御肠道细菌感染的重要保护机制之一，推测促进肠黏膜上皮更新和损伤修复，能够提高宿主的感染耐受能力。以往利用c-kit功能丢失突变wadsm/m小鼠，我们已证明肠腺细胞表达的KIT分子能够促进肠黏膜上皮的增殖和更新，但是否参与肠黏膜上皮感染耐受的调控尚不清楚。本项目拟利用野生型和wadsm/m小鼠，结合形态学、分子生物学和活体影像检测细菌负载等方法，研究肠黏膜上皮KIT受体是否通过如下途径调控宿主的感染耐受：（1）直接激活下游STATs或Akt分子，促进肠黏膜上皮增殖、更新和损伤修复；（2）通过ERK1/2转录因子调控TLR-2受体表达，间接促进肠黏膜上皮的增殖和更新，共同发挥提高肠黏膜上皮感染耐受的作用。本研究期望能够阐明KIT分子对肠道细菌感染耐受的调控机制，为临床预防肠源性感染等疾病提供新的思路。

In 2007, R?berg. et al proposed that infection tolerance is one of the important protection mechanisms for host to defense against intestinal bacterial infections and speculated that increasing intestinal epithelial renewal and damage repair capacity may promote the infection tolerance. We recently have shown that KIT is expressed in the intestinal gland cells using a loss-of-function mutation of the mouse W/c-kit locus, wadsm/m mice and found that it was able to promote intestinal epithelial proliferation and renewal. However, whether KIT in the intestinal epithelium is involved in infection tolerance was unclear. In this project, we will investigate the contribution of KIT to tolerance response against bacterial pathogen in the gut using WT and wadsm/m mice combined with morphological, molecular biological, and in vivo imaging methods. We will focus on the two following subjects :(1)KIT signaling improves the intestinal epithelial proliferation, renew, and damage repair by direct activation of downstream of STATs or Akt molecules; (2) KIT signaling enhances the proliferation and renew of the intestinal epithelium by indirect upregulation of the TLR-2 receptor gene expression through the ERK1/2 transcription factor. They may synergistically improve intestinal epithelial infection tolerance. This study aims to clarify the molecular regulation mechanism of intestinal bacterial infection tolerance and provide a clue to the clinicians for the prevention of enterogenic infection diseases.