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新闻资讯

Nlrp9b炎症小体抵御肠胃病毒

发布时间:2017-07-17 浏览次数:656

信息来源:
http://www.natureasia.com/zh-cn/nature/highlights/86956
https://www.nature.com/nature/journal/v546/n7660/full/nature22967.html

轮状病毒可在幼儿中引起时有致命的严重胃肠疾病。 人们对这种肠病毒在体内如何被探测和控制还所知甚少。Richard Flavell及同事报告表明,通过RNA解旋酶Dhx9,炎症小体受体Nlrp9能与双链病毒RNA相互作用,帮助抵抗肠病毒。这种作用能对受感染细胞触发Gasdermin D蛋白依赖性细胞焦亡,并引起IL-18分泌。这种固有免疫信号转导只在肠上皮细胞中起作用,或能揭示出调控病毒防御的有用靶标。

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells

Shu Zhu,Siyuan Ding,Penghua Wang,Zheng Wei,Wen Pan,Noah W. Palm,Yi Yang,Hua Yu, Hua-Bing Li,Geng Wang,Xuqiu Lei, Marcel R. de Zoete,Jun Zhao,Yunjiang Zheng, Haiwei Chen,Yujiao Zhao,Kellie A. Jurado,Ningguo Feng,Liang Shan, Yuval Kluger,Jun Lu,Clara Abraham,Erol Fikrig, Harry B. Greenberg & Richard A. Flavell

Nature 546, 667–670 (29 June 2017) doi:10.1038/nature22967

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide1. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling2, 3, 4, 5, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.