Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production
Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production
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DOI：
10.1038/ni.1824
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发表时间：
2010-01-01
影响因子：
30.5
通讯作者：
Ruland, Juergen
中科院分区：
文献类型：
--
作者：
Poeck, Hendrik;Bscheider, Michael;Ruland, Juergen
白细胞介素1 β（IL-1 β）是病毒感染过程中一种有效的促炎因子。它的产生受到依赖于转录因子NF-κ B的IL 1 B转录和随后由炎性小体加工前IL-1 β的严格控制。然而，促进RNA病毒诱导的IL-1 β产生的传感器和机制尚未明确。在这里，我们报告了RNA解旋酶RIG-I在RNA病毒诱导的促炎反应中的双重作用。尽管RIG-I介导的NF-κ B活化需要信号传导衔接子MAVS和衔接子CARD 9和Bcl-10的复合物，但RIG-I还结合衔接子ASC以通过独立于MAVS、CARD 9和Nod样受体蛋白NLRP 3的机制触发半胱天冬酶-1依赖性炎性小体活化。我们的研究结果确定了CARD 9-Bcl-10模块作为RIG-I依赖性促炎反应的重要组成部分，并建立了RIG-I作为能够激活炎性小体以响应某些RNA病毒的传感器。
Interleukin 1 beta (IL-1 beta) is a potent proinflammatory factor during viral infection. Its production is tightly controlled by transcription of Il1b dependent on the transcription factor NF-kappa B and subsequent processing of pro-IL-1 beta by an inflammasome. However, the sensors and mechanisms that facilitate RNA virus-induced production of IL-1 beta are not well defined. Here we report a dual role for the RNA helicase RIG-I in RNA virus-induced proinflammatory responses. Whereas RIG-I-mediated activation of NF-kappa B required the signaling adaptor MAVS and a complex of the adaptors CARD9 and Bcl-10, RIG-I also bound to the adaptor ASC to trigger caspase-1-dependent inflammasome activation by a mechanism independent of MAVS, CARD9 and the Nod-like receptor protein NLRP3. Our results identify the CARD9-Bcl-10 module as an essential component of the RIG-I-dependent proinflammatory response and establish RIG-I as a sensor able to activate the inflammasome in response to certain RNA viruses.