Nature:Nlrp9b炎性体限制轮状病毒在肠上皮细胞的感染

2017-06-22 MedSci MedSci原创

轮状病毒,是幼儿严重肠胃炎和腹泻的主要起因,每年全世界范围内约有215000人死于其感染。轮状病毒专门感染宿主小肠的肠上皮细胞,并进化出策略,对抗干扰素和NF-κB信号,这使得人们也提出疑问-是否有其他宿主因子在肠粘膜上参与抗病毒反应。肠病毒在体内特别是被NOD样受体炎性体感知和限制的机制依然不明。本研究报道了一个NOD样受体Nlrp9b-它的表达表现出肠上皮细胞高度专一性,并详细描述了其限制轮状

轮状病毒,是幼儿严重肠胃炎和腹泻的主要起因,每年全世界范围内约有215000人死于其感染。轮状病毒专门感染宿主小肠的肠上皮细胞,并进化出策略,对抗干扰素和NF-κB信号,这使得人们也提出疑问-是否有其他宿主因子在肠粘膜上参与抗病毒反应。肠病毒在体内特别是被NOD样受体炎性体感知和限制的机制依然不明。本研究报道了一个NOD样受体Nlrp9b-它的表达表现出肠上皮细胞高度专一性,并详细描述了其限制轮状病毒感染的机制。研究结果表明,Nlrp9b通过RNA解旋酶Dhx9识别短双链RNA延伸,并与适配子Asc和caspase-1一起形成炎性体复合物,以此促进干扰素18的成熟和Gsdmd诱导的炎症坏死(后者可以诱导感染的肠上皮细胞早死亡及维持肠稳态,以此在宿主限制轮状病毒复制中发挥特别重要的作用)。同时研究表明,在体内条件性敲除肠道上的Nlrp9b或其他炎性体成分,导致小鼠对轮状病毒复制的易感性增加。

本研究使用轮状病毒感染作为模型,全面阐释和解析了一个新的NOD样受体Nlrp9b(被IEC专一性表达)在宿主对抗肠病毒感染中发挥的作用。这项研究将为调整宿主抵抗病毒病原提供有效的靶点。

原始出处:

Shu Zhu, et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature, 2017 Jun.doi:10.1038/nature22967

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    2018-05-07 liye789132251
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    2017-06-24 yuandd
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