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首页> 外文期刊>Infection and immunity >Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis
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Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis

机译：MyD88介导的嗜中性粒细胞募集在艰难梭菌结肠炎中的关键作用。

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Clostridium difficile can infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. Little is known about the innate immune signaling pathways that marshal inflammatory responses to C. difficile infection and whether protective and pathogenic inflammatory responses can be dissociated. Toll-like receptors predominantly signal via the MyD88 adaptor protein and are important mediators of innate immune signaling in the intestinal mucosa. Here, we demonstrate that MyD88-mediated signals trigger neutrophil and CCR2-dependent Ly6Chi monocyte recruitment to the colonic lamina propria (cLP) during infection, which prevent dissemination of bystander bacteria to deeper tissues. Mortality is markedly increased in MyD88-deficient mice following C. difficile infection, as are parameters of mucosal tissue damage and inflammation. Antibody-mediated depletion of neutrophils markedly increases mortality, while attenuated recruitment of Ly6Chi monocytes in CCR2-deficient mice does not alter the course of C. difficile infection. Expression of CXCL1, a neutrophil-recruiting chemokine, is impaired in the cLP of MyD88?/? mice. Our studies suggest that MyD88-mediated signals promote neutrophil recruitment by inducing expression of CXCL1, thereby providing critical early defense against C. difficile-mediated colitis.
机译：当通过施用抗生素改变正常的肠道菌群时，艰难梭菌可感染大肠并引起结肠炎。关于固有的免疫信号途径，这些疾病封送了对艰难梭菌感染的炎性反应，以及保护性和病原性炎性反应是否可以被分离，人们所知甚少。 Toll样受体主要通过MyD88衔接蛋白发出信号，并且是肠道粘膜固有免疫信号的重要介体。在这里，我们证明MyD88介导的信号在感染过程中触发嗜中性粒细胞和CCR2依赖的Ly6Chi单核细胞募集到结肠固有层（cLP），从而阻止旁观者细菌传播到更深的组织。艰难梭菌感染后，MyD88缺陷型小鼠的死亡率显着增加，粘膜组织损伤和炎症的参数也显着增加。抗体介导的嗜中性白细胞耗竭明显增加了死亡率，而CCR2缺陷型小鼠中Ly6Chi单核细胞的募集减弱却不会改变艰难梭菌的感染过程。嗜中性粒细胞趋化因子CXCL1的表达在MyD88？/？的cLP中受损。老鼠。我们的研究表明，MyD88介导的信号通过诱导CXCL1的表达促进嗜中性白细胞的募集，从而为艰难梭菌介导的结肠炎提供了关键的早期防御。

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