Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiaotong University School of Medicine, Shanghai, China.
Cell Signal. 2013 Sep;25(9):1887-94. doi: 10.1016/j.cellsig.2013.05.020. Epub 2013 May 23.
Immune responses to pathogens are regulated by immune receptors containing either an immunoreceptor tyrosine-based activation motif (ITAM) or an immunoreceptor tyrosine-based inhibitory motif (ITIM). The important diarrheal pathogen enteropathogenic Escherichia coli (EPEC) require delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane for pedestal formation. The C-terminal region of Tir, encompassing Y483 and Y511, shares sequence similarity with cellular ITIMs. Here, we show that EPEC Tir suppresses the production of inflammatory cytokines by recruitment of SHP-2 and subsequent deubiquitination of TRAF6 in an ITIM dependent manner. Our findings revealed a novel mechanism by which the EPEC utilize its ITIM motifs to suppress and evade the host innate immune response, which could lead to the development of novel therapeutics to prevent bacterial infection.
免疫受体含有免疫受体酪氨酸激活基序（ITAM）或免疫受体酪氨酸抑制基序（ITIM），可调节对病原体的免疫反应。重要的腹泻病原体肠致病性大肠杆菌（EPEC）需要将细菌易位紧密素受体（Tir）递送至并插入宿主质膜中以形成基脚。Tir 的 C 末端区域，包含 Y483 和 Y511，与细胞 ITIM 具有序列相似性。在这里，我们表明 EPEC Tir 通过募集 SHP-2 并随后以 ITIM 依赖性方式去泛素化 TRAF6 来抑制炎性细胞因子的产生。我们的发现揭示了 EPEC 利用其 ITIM 基序抑制和逃避宿主固有免疫反应的新机制，这可能导致开发预防细菌感染的新型治疗方法。
