A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity

作者：Negishi Hideo; Osawa Tomoko; Ogami Kentaro; Ouyang Xinshou; Sakaguchi Shinya; Koshiba Ryuji; Yanai Hideyuki; Seko Yoshinori; Shitara Hiroshi; Bishop Keith; Yonekawa Hiromichi; Tamura Tomohiko; Kaisho Tsuneyasu; Taya Choji; Taniguchi Tadatsugu^*; Honda Kenya

来源：Proceedings of the National Academy of Sciences, 2008, 105(51): 20446-20451.

DOI：10.1073/pnas.0810372105

• antiviral response
• coxsackievirus
• cytokine
• IFN-gamma
• Toll-like receptor 3

A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 receptors cooperate during virus infection. The conventional wisdom has been that the activation of these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role of a Toll-like receptor 3 (TLR3)-dependent type II IFN signaling pathway in antiviral innate immune response against Coxsackievirus group B serotype 3 (CVB3), a member of the positive-stranded RNA virus family picornaviridae and most prevalent virus associated with chronic dilated cardiomyopathy. TLR3-deficient mice show a vulnerability to CVB3, accompanied by acute myocarditis, whereas transgenic expression of TLR3 endows even type I IFN signal-deficient mice resistance to CVB3 and other types of viruses, provided that type II IFN signaling remains intact. Taken together, our results indicate a critical cooperation of the RIG-I/MDA5-type I IFN and the TLR3-type II IFN signaling axes for efficient innate antiviral immune responses.

• 出版日期2008-12-23
• 单位河北医科大学