Nlrp6 regulates intestinal antiviral innate immunity.
Nlrp6 regulates intestinal antiviral innate immunity.
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DOI：
10.1126/science.aab3145
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发表时间：
2015-11-13
期刊：
影响因子：
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通讯作者：
Fikrig E
中科院分区：
文献类型：
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作者：
Wang P;Zhu S;Yang L;Cui S;Pan W;Jackson R;Zheng Y;Rongvaux A;Sun Q;Yang G;Gao S;Lin R;You F;Flavell R;Fikrig E
核苷酸结合寡聚结构域样受体（Nlrp） 6维持肠道微生物群稳态并调节抗菌免疫。我们现在报道了Nlrp6在控制肠道病毒感染中的作用。Nlrp6−/−和对照组的脑心肌炎病毒全身攻击小鼠具有相似的死亡率，然而，Nlrp6−/−小鼠的胃肠道表现出增加的病毒载量。与对照组相比，口服感染脑心肌炎病毒的Nlrp6 - / -小鼠死亡率和病毒血症增加。在小鼠诺如病毒1中也观察到类似的结果。Nlrp6通过RNA解旋酶Dhx15结合病毒RNA，并与Mavs相互作用诱导I/III型干扰素（IFNs）和ifn刺激基因（ISGs）。这些数据表明Nlrp6与Dhx15一起作为病毒RNA传感器诱导isg，并且这种作用在肠道中尤为重要。
The nucleotide-binding oligomerization domain-like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6−/− and control mice systemically challenged with encephalomyocarditis virus had similar mortality, however, the gastrointestinal tract of Nlrp6−/− mice exhibited increased viral loads. Nlrp6−/− mice orally infected with encephalomyocarditis virus had increased mortality and viremia compared to controls. Similar results were observed with murine norovirus 1. Nlrp6 bound viral RNA via the RNA helicase Dhx15 and interacted with Mavs to induce type I/III interferons (IFNs) and IFN-stimulated genes (ISGs). These data demonstrate that Nlrp6 functions with Dhx15 as a viral RNA sensor to induce ISGs, and this effect is especially important in the intestinal tract.