Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.
复制标题
NLRP9B炎性体限制了肠上皮细胞中的轮状病毒感染。
DOI：
10.1038/nature22967
复制
发表时间：
2017-06-29
期刊：
影响因子：
64.8
通讯作者：
Flavell RA
中科院分区：
文献类型：
--
作者：
Zhu S;Ding S;Wang P;Wei Z;Pan W;Palm NW;Yang Y;Yu H;Li HB;Wang G;Lei X;de Zoete MR;Zhao J;Zheng Y;Chen H;Zhao Y;Jurado KA;Feng N;Shan L;Kluger Y;Lu J;Abraham C;Fikrig E;Greenberg HB;Flavell RA
轮状病毒是幼儿严重胃肠炎和腹泻的主要病因，在全球每年导致约21.5万人死亡。轮状病毒专门感染宿主小肠中的肠上皮细胞，并已进化出拮抗干扰素和NF - κB信号传导的策略，这就提出了一个问题：是否其他宿主因子参与肠黏膜的抗病毒反应。肠道病毒在体内被感知和限制的机制，特别是被NOD样受体（NLR）炎症小体感知和限制的机制，在很大程度上是未知的。在此，我们发现了NLR Nlrp9b并对其机制进行了表征，它在肠上皮细胞中特异性表达并限制轮状病毒感染。我们的数据显示，通过RNA解旋酶Dhx9，Nlrp9b识别短的双链RNA片段，并与衔接蛋白Asc和半胱天冬酶 - 1形成炎症小体复合物，以促进白细胞介素（Il）- 18的成熟和由gasdermin D（Gsdmd）诱导的细胞焦亡。在体内肠道中对Nlrp9b或其他炎症小体成分进行条件性耗竭，导致小鼠对轮状病毒复制的易感性增强。我们的研究强调了一种在肠上皮细胞中起作用的重要先天免疫信号通路，并且可能为调节宿主对病毒病原体的防御提供有用的靶点。
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, 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.
登录
查看更多内容
DOI：
10.1126/science.aaf7532
发表时间：
2016-11-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hu B;Jin C;Li HB;Tong J;Ouyang X;Cetinbas NM;Zhu S;Strowig T;Lam FC;Zhao C;Henao-Mejia J;Yilmaz O;Fitzgerald KA;Eisenbarth SC;Elinav E;Flavell RA
通讯作者：
Flavell RA
NLRC4在肠上皮细胞中的表达介导了针对肠道病原体的保护。
影响因子：
8
作者：
通讯作者：
--
影响因子：
6.7
作者：
Ding S;Mooney N;Li B;Kelly MR;Feng N;Loktev AV;Sen A;Patton JT;Jackson PK;Greenberg HB
通讯作者：
Greenberg HB
影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
影响因子：
64.5
作者：
Levy M;Thaiss CA;Zeevi D;Dohnalová L;Zilberman-Schapira G;Mahdi JA;David E;Savidor A;Korem T;Herzig Y;Pevsner-Fischer M;Shapiro H;Christ A;Harmelin A;Halpern Z;Latz E;Flavell RA;Amit I;Segal E;Elinav E
通讯作者：
Elinav E