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首页> 外文期刊>Infection and immunity >Attaching and Effacing Bacterial Effector NleC Suppresses Epithelial Inflammatory Responses by Inhibiting NF-κB and p38 Mitogen-Activated Protein Kinase Activation
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Attaching and Effacing Bacterial Effector NleC Suppresses Epithelial Inflammatory Responses by Inhibiting NF-κB and p38 Mitogen-Activated Protein Kinase Activation

机译：附着和修饰细菌效应子NleC通过抑制NF-κB和p38丝裂原激活的蛋白激酶激活抑制上皮炎症反应。

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Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli are noninvasive attaching and effacing (A/E) bacterial pathogens that cause intestinal inflammation and severe diarrheal disease. These pathogens utilize a type III secretion system to deliver effector proteins into host epithelial cells, modulating diverse cellular functions, including the release of the chemokine interleukin-8 (IL-8). While studies have implicated the effectors NleE (non-locus of enterocyte effacement [LEE]-encoded effector E) and NleH1 in suppressing IL-8 release, by preventing NF-κB nuclear translocation, the impact of these effectors only partially replicates the immunosuppressive actions of wild-type EPEC, suggesting another effector or effectors are involved. Testing an array of EPEC mutants, we identified the non-LEE-encoded effector C (NleC) as also suppressing IL-8 release. Infection by ΔnleC EPEC led to exaggerated IL-8 release from infected Caco-2 and HT-29 epithelial cells. NleC localized to EPEC-induced pedestals, with signaling studies revealing NleC inhibits both NF-κB and p38 mitogen-activated protein kinase (MAPK) activation. Using Citrobacter rodentium, a mouse-adapted A/E bacterium, we found that ΔnleC and wild-type C. rodentium-infected mice carried similar pathogen burdens, yet ΔnleC strain infection led to worsened colitis. Similarly, infection with ΔnleC C. rodentium in a cecal loop model induced significantly greater chemokine responses than infection with wild-type bacteria. These studies thus advance our understanding of how A/E pathogens subvert host inflammatory responses.
机译：肠致病性大肠杆菌（EPEC）和肠出血性大肠杆菌是引起肠炎症和严重腹泻病的无创附着和消灭（A / E）细菌病原体。这些病原体利用III型分泌系统将效应蛋白传递到宿主上皮细胞中，调节多种细胞功能，包括释放趋化因子白介素8（IL-8）。尽管研究表明效应子NleE（非肠上皮细胞浸没[LEE]编码的效应子E）和NleH1通过阻止NF-κB核移位来抑制IL-8释放，但这些效应子的作用仅部分复制了免疫抑制作用野生型EPEC的表达，提示涉及其他一个或多个效应子。通过测试一系列EPEC突变体，我们确定了非LEE编码的效应子C（NleC）也抑制了IL-8的释放。 Δ nleC EPEC的感染导致感染的Caco-2和HT-29上皮细胞IL-8释放过大。 NleC定位于EPEC诱导的基座，信号研究表明NleC抑制NF-κB和p38丝裂原激活的蛋白激酶（MAPK）激活。使用适合小鼠的A / E细菌啮齿类柠檬酸杆菌，我们发现Δ nleC 和野生型感染了C.rodenium的小鼠携带相似的病原体负担，而Δ nleC 菌株感染导致结肠炎恶化。同样，盲肠环模型中的Δ nleC 啮齿类动物感染比野生型细菌感染诱导的趋化因子应答明显更大。因此，这些研究提高了我们对A / E病原体如何破坏宿主炎症反应的理解。

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