Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis.
Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis.
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DOI：
10.1016/j.chom.2013.08.003
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发表时间：
2013-09-11
影响因子：
30.3
通讯作者：
Belkaid Y
中科院分区：
文献类型：
--
作者：
Molloy MJ;Grainger JR;Bouladoux N;Hand TW;Koo LY;Naik S;Quinones M;Dzutsev AK;Gao JL;Trinchieri G;Murphy PM;Belkaid Y
共生菌群组成的变化正在成为胃肠道炎症的标志。特别是，γ-变形菌的生长与炎症性肠病的病因和感染的病理后果有关。在这里，我们表明，胃肠道感染后，共生产物的控制是一个高度协调的过程，涉及宿主反应和微生物信号。值得注意的是，中性粒细胞向管腔的迁移导致有组织的管腔内结构的产生，这些结构包裹了共生体并限制了它们与上皮的接触。这些腔型的形成取决于高亲和力的n -甲酰基肽受体Fpr1。因此，感染后，缺乏Fpr1的小鼠表现出微生物易位增加，共栖遏制能力差，死亡率增加。总之，我们目前的研究描述了一种新的机制，通过这种机制，宿主在感染期间迅速遏制共生病原体的生长。此外，这些结果表明Fpr1在生态失调期间是宿主共生相互作用的主要介质。
Shifts in the composition of the commensal microbiota are emerging as a hallmark of gastrointestinal inflammation. In particular, outgrowth of γ-proteobacteria has been linked to the etiology of inflammatory bowel disease and the pathologic consequences of infections. Here we show that, following gastrointestinal infection, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals. Notably, neutrophil emigration to the lumen results in the generation of organized intra-luminal structures that encapsulate commensals and limit their contact with the epithelium. Formation of these luminal casts depends upon the high-affinity N-formyl peptide receptor, Fpr1. Consequently, after infection, mice deficient in Fpr1 display increased microbial translocation, poor commensal containment and increased mortality. Altogether, our present study describes a novel mechanism by which the host rapidly contains outgrowth of commensal pathobionts during infection. Further, these results reveal Fpr1 as a major mediator of host commensal interaction during dysbiosis.