輪狀病毒可在幼兒中引起時有致命的嚴重胃腸疾病。 人們對這種腸病毒在體內如何被探測和控制還所知甚少。Richard Flavell及同事報告表明,通過RNA解旋酶Dhx9,炎癥小體受體Nlrp9能與雙鏈病毒RNA相互作用,幫助抵抗腸病毒。這種作用能對受感染細胞觸發Gasdermin D蛋白依賴性細胞焦亡,并引起IL-18分泌。這種固有免疫信號轉導只在腸上皮細胞中起作用,或能揭示出調控病毒防御的有用靶標。

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.