讲座题目: Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs

主讲人: 严大鹏🧎‍♀️‍➡️，哈佛大学医天美微生物与免疫学系博士后

主持人:赖玉平 教授

开始时间:2015-3-4 13:30

讲座地址:闵行生科院534报告厅

 

报告人简介：严大鹏博士🩳，2007年获得同济大学生命科学与技术天美学士学位🪭，2013年获得中科院上海生命科天美健康所博士学位，2013年7月至今在哈佛大学医天美微生物与免疫学系做博士后研究🤦🏻‍♂️，师从国际著名免疫学家Diane Mathis和Christophe Benoist教授（两人均为美国科天美院士），从事调节性T细胞信号转导研究🌠。

 

报告摘要：The protein Tir (translocated intimin receptor) in enteric bacteria shares sequence similarity with the host cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). Despite the importance of Tir in pedestal formation, relatively little is known about the role of Tir and its ITIMs in the regulation of the host immune response. Here we demonstrate that Tir from enteropathogenic Escherichia coli (EPEC) interacted with the host cellular tyrosine phosphatase SHP-1 in an ITIM phosphorylation–dependent manner. The association of Tir with SHP-1 facilitated the recruitment of SHP-1 to the adaptor TRAF6 and inhibited the ubiquitination of TRAF6. Moreover, the ITIMs of Tir suppressed EPEC-stimulated expression of proinflammatory cytokines and inhibited intestinal immunity to infection with Citrobacter rodentium. Our findings identify a previously unknown mechanism by which bacterial ITIM-containing proteins can inhibit innate immune responses.