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首页> 外文期刊>Infection and immunity >Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection
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Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection

机译：Tir触发啮齿动物柠檬酸杆菌感染过程中肠细胞和中性粒细胞募集中CXCL1的表达

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摘要

The hallmarks of enteropathogenic Escherichia coli (EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen Citrobacter rodentium. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in C. rodentium colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to C. rodentium infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a C. rodentium strain expressing Tir_Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with C. rodentium expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to C. rodentium infection.
机译：肠致病性大肠杆菌（EPEC）感染的标志是在粘膜表面形成附着和消融（A / E）损伤，在培养细胞上形成富含肌动蛋白的基座，这两者都依赖于III型分泌系统效应物Tir。易位到培养细胞中并被内膜蛋白簇集后，Tir Y474被磷酸化，导致Nck募集，N-WASP活化和肌动蛋白通过Arp2 / 3复合物聚合。次要的，弱的肌动蛋白聚合途径是通过NPY基序（Y454）触发的。重要的是，Y454和Y474在被EPEC样小鼠病原体啮齿类柠檬酸杆菌感染后在粘膜表面的A / E病变形成中不起作用。在这项研究中，我们调查了Cir啮齿动物定居和A / E病变形成中位于Y451上游和Y471下游的Tir区段的作用。我们还测试了Tir残基Y451和Y471在宿主对啮齿类念珠菌感染的免疫反应中的作用。我们发现，氨基酸382-462或478-547的缺失对Tir介导A / E病变形成的能力没有影响，尽管氨基酸478-547的缺失影响了Tir的转运。从感染小鼠分离的肠上皮细胞的检查表明，表达Tir_Y451A / Y471A的啮齿类念珠菌菌株在结肠中招募的中性粒细胞明显少于野生型菌株，并且在感染后第14天引起的结肠增生更少。一致地，从感染了表达Tir_Y451A / Y471A的啮齿类杆菌的小鼠分离的肠上皮细胞表达的CXCL1明显减少。这些结果表明，Tir诱导的肌动蛋白重塑在调节对啮齿类杆菌感染的免疫反应中起直接作用。

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