Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production

Hendrik Poeck et al. Nature immunology 11: 63-71 (2010)

Student:  Chih-Yuan Kuo (郭芝源）             Time: 14:00~15:00, Mar. 24, 2010

Commentator: Dr. Pin Ling (凌斌老師）   Place: Room 601

Abstract:

Intracellular viral sensors play an important role in initiating innate antiviral response and proinflammatory cytokine production. Cytoplasmic viral sensors including RIG-I, Mda5 and LGP2, which belong to RIG-I like receptor family (RLRs), were reported to recognize specific viral RNA, trigger type I IFN production and NF-κB activation¹. On the other hand, proinflammatory cytokine IL-1β production require NF-κB activation and inflammasome formation, which are responsible for pro-IL-1β production and caspase-1 activation, respectively. Caspase-1 is a proteolytic enzyme that cleaves pro-IL-1β into mature IL-1β². However, the mechanism about RLR-induced IL-1β production is not well defined. In this study, the authors found that VSV and RIG-I agonist 3pRNA both induce mature IL-1β production, NF-κB activation and procaspase-1 cleavage. Besides, the authors further used macrophages derived from MAVS or RIG-I knock-out mice to separate RIG-I-induced, MAVS-mediated NF-κB activation from RIG-I-mediated procaspase-1 cleavage. The authors also found that RIG-I engages the CARD9–Bcl-10 module for NF-κB activation. Furthermore, they found that RIG-I-triggered caspase-1 cleavage was mediated by RIG-I/ASC inflammasome complex rather than NLRP3 inflammasome. The results indicated that RIG-I directly engages ASC for inflammasome activation and caspase-1 maturation. In conclusion, this study identified that RIG-I serves as a dual role that can trigger both CARD9–Bcl-10-dependent pro-IL-1β production and ASC-dependent inflammasome activation.

References:

1.      Mitsutoshi Y. et al. Function of RIG-I-like receptors in antiviral innate immunity. J.B.C. 282:15315–15318 (2007)

2. Clare B. et al. Molecular mechanisms involved in inflammasome activation. Trends in Cell Biology 19:455-464 (2009)