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首页> 外文期刊>Nature immunology >Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs
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Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs

机译：含有基于免疫受体酪氨酸的抑制性基序的细菌蛋白对TLR信号的抑制

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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.
机译：肠细菌中的蛋白质Tir（易位的intimin受体）与基于宿主细胞免疫受体酪氨酸的抑制基序（ITIM）具有序列相似性。尽管Tir在基座形成中很重要，但对Tir及其ITIM在调节宿主免疫反应中的作用了解甚少。在这里，我们证明来自肠致病性大肠杆菌（EPEC）的Tir以ITIM磷酸化依赖性方式与宿主细胞酪氨酸磷酸酶SHP-1相互作用。 Tir与SHP-1的结合促进了SHP-1向衔接子TRAF6的募集，并抑制了TRAF6的泛素化。此外，Tir的ITIM抑制了EPEC刺激的促炎性细胞因子的表达，并抑制了肠道对啮齿类柠檬酸杆菌感染的免疫力。我们的发现确定了以前未知的机制，细菌含ITIM的蛋白质可通过该机制抑制先天免疫应答。

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