Nlrp6 regulates intestinal antiviral innate immunity,Science

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Nlrp6 regulates intestinal antiviral innate immunity
Science ( IF 44.7 ) Pub Date : 2015-10-22 , DOI: 10.1126/science.aab3145
Penghua Wang _{1,

2} , Shu Zhu ₃ , Long Yang _{1,

2} , Shuang Cui ₁ , Wen Pan ₄ , Ruaidhri Jackson ₃ , Yunjiang Zheng ₃ , Anthony Rongvaux ₃ , Qiangming Sun ₁ , Guang Yang ₁ , Shandian Gao ₁ , Rongtuan Lin ₅ , Fuping You ₁ , Richard Flavell _{3,

6} , Erol Fikrig _{1,

6}

Affiliation

Nlrp6 keeps gut infections in check Most viruses infect only certain cells of the body. Enteric viruses, such as norovirus and rotavirus, specifically infect the gut. Wang et al. now show that the response to such viruses is tissue-specific, too. Antiviral immunity to enteric but not systemic viral infections in mice required Nlrp6, a member of the NOD-like receptor family of proteins that play important roles in host defense. Together with the RNA helicase protein Dhx15, Nlrp6 bound viral RNA and elicited downstream antiviral immune responses necessary for viral clearance. These included the production of type I and type III interferons and the expression of interferon-stimulated genes. Science, this issue p. 826 Control of gut but not systemic viral infections in mice requires the protein NLRP6. 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 with controls. Similar results were observed with murine norovirus 1. Nlrp6 bound viral RNA via the RNA helicase Dhx15 and interacted with mitochondrial antiviral signaling protein 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.

中文翻译：

Nlrp6调节肠道抗病毒先天免疫

Nlrp6 控制肠道感染大多数病毒只感染身体的某些细胞。肠道病毒，如诺如病毒和轮状病毒，专门感染肠道。王等人。现在表明对此类病毒的反应也是组织特异性的。小鼠肠道病毒感染而非全身病毒感染的抗病毒免疫需要 Nlrp6，Nlrp6 是 NOD 样受体蛋白家族的成员，在宿主防御中起重要作用。Nlrp6 与 RNA 解旋酶蛋白 Dhx15 一起结合病毒 RNA 并引发病毒清除所需的下游抗病毒免疫反应。其中包括 I 型和 III 型干扰素的产生以及干扰素刺激基因的表达。科学，这个问题 p。826 控制小鼠肠道而非全身性病毒感染需要蛋白质 NLRP6。核苷酸结合寡聚化结构域样受体 (Nlrp) 6 维持肠道微生物群稳态并调节抗菌免疫。我们现在报告 Nlrp6 在控制肠道病毒感染中的作用。Nlrp6-/- 和用脑心肌炎病毒全身攻击的对照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-/- 小鼠的死亡率和病毒血症增加。在鼠诺如病毒 1 中观察到类似的结果。 Nlrp6 通过 RNA 解旋酶 Dhx15 结合病毒 RNA，并与线粒体抗病毒信号蛋白相互作用以诱导 I/III 型干扰素 (IFN) 和 IFN 刺激基因 (ISG)。

更新日期：2015-10-22

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