Critical Role for Cryopyrin/Nalp3 in Activation of Caspase-1 in Response to Viral Infection and Double-stranded RNA

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阅读量：

143

作者：

TD Kanneganti，M Body-Malapel，A Amer，JH Park，J Whitfield，L Franchi，ZF Taraporewala，D Miller，JT Patton，N Inohara

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摘要：

Viral infection induces the production of interleukin (IL)-1β and IL-18 in macrophages through the activation of caspase-1, but the mechanism by which host cells sense viruses to induce caspase-1 activation is unknown. In this report, we have identified a signaling pathway leading to caspase-1 activation that is induced by double-stranded RNA (dsRNA) and viral infection that is mediated by Cryopyrin/Nalp3. Stimulation of macrophages with dsRNA, viral RNA, or its analog poly(I:C) induced the secretion of IL-1β and IL-18 in a cryopyrin-dependent manner. Consistently, caspase-1 activation triggered by poly(I:C), dsRNA, and viral RNA was abrogated in macrophages lacking cryopyrin or the adaptor ASC ( a poptosis-associated s peck-like protein containing a c aspase-activating and recruitment domain) but proceeded normally in macrophages deficient in Toll-like receptor 3 or 7. We have also shown that infection with Sendai and influenza viruses activates the cryopyrin inflammasome. Finally, cryopyrin was required for IL-1β production in response to poly(I:C) in vivo . These results identify a mechanism mediated by cryopyrin and ASC that links dsRNA and viral infection to caspase-1 activation resulting in IL-1β and IL-18 production.

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关键词：

Critical Cryopyrin/Nalp Activation Caspase Response Infection Doublestranded

DOI：

10.1074/jbc.M607594200

被引量：

1658

年份：

2006