Microbiota-Dependent Priming of Antiviral Intestinal Immunity in Drosophila.
Microbiota-Dependent Priming of Antiviral Intestinal Immunity in Drosophila.
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DOI：
10.1016/j.chom.2015.10.010
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发表时间：
2015-11-11
影响因子：
30.3
通讯作者：
Cherry S
中科院分区：
文献类型：
--
作者：
Sansone CL;Cohen J;Yasunaga A;Xu J;Osborn G;Subramanian H;Gold B;Buchon N;Cherry S
肠道病原体必须克服肠道防御才能建立感染。在果蝇中，ERK信号通路抑制肠道病毒感染。肠道菌群也影响免疫力，但其在肠道病毒感染中的作用尚不清楚。在这里，我们发现两个信号需要激活肠上皮中的抗病毒ERK信号。一种信号依赖于微生物群对肽聚糖的识别，特别是来自共生的臭醋杆菌，它启动了nf - kb依赖性的分泌因子Pvf2的诱导。然而，微生物群不足以诱导这一途径；由Cdk9激酶介导的转录暂停基因的释放也是Pvf2产生所必需的第二种病毒启动信号。Pvf2通过与受体酪氨酸激酶PVR结合来刺激抗病毒免疫，这是肠道ERK反应的必要和充分条件。这些发现表明，对特定共生体的感知启动了限制肠道病毒感染的上皮反应所需的炎症信号。
Enteric pathogens must overcome intestinal defenses to establish infection. In Drosophila, the ERK signaling pathway inhibits enteric virus infection. The intestinal microflora also impacts immunity but its role in enteric viral infection is unknown. Here we show that two signals are required to activate antiviral ERK signaling in the intestinal epithelium. One signal depends on recognition of peptidoglycan from the microbiota, particularly from the commensal Acetobacter pomorum, which primes the NF-kB-dependent induction of a secreted factor, Pvf2. However, the microbiota is not sufficient to induce this pathway; a second virus-initiated signaling involving release of transcriptional paused genes mediated by the kinase Cdk9 is also required for Pvf2 production. Pvf2 stimulates antiviral immunity by binding to the receptor tyrosine kinase PVR, which is necessary and sufficient for intestinal ERK responses. These findings demonstrate that sensing of specific commensals primes inflammatory signaling required for epithelial responses that restrict enteric viral infections.