III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Nat Immunol. 2010 Jan;11(1):63-9. doi: 10.1038/ni.1824. Epub 2009 Nov 15.
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-kappaB 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-kappaB 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.
白细胞介素 1β（IL-1β）是病毒感染期间一种有效的促炎因子。其产生受到转录因子 NF-κB 依赖的 Il1b 转录的严格控制，随后由炎症小体对前体 IL-1β进行加工。然而，促进 RNA 病毒诱导产生 IL-1β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。虽然 RIG-I 介导的 NF-κB 激活需要信号适配器 MAVS 和适配器 CARD9 和 Bcl-10 的复合物，但 RIG-I 还与适配器 ASC 结合，通过一种独立于 MAVS、CARD9 和 Nod 样受体蛋白 NLRP3 的机制触发 caspase-1 依赖性炎症小体激活。我们的结果确定了 CARD9-Bcl-10 模块是 RIG-I 依赖性促炎反应的必需组成部分，并确立了 RIG-I 作为一种能够响应某些 RNA 病毒激活炎症小体的传感器。
