1. A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity
- Author
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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, and Honda, Kenya
- Subjects
Cellular signal transduction -- Research ,Immune response -- Research ,Interferon -- Physiological aspects ,Interferon -- Health aspects ,Cell receptors -- Physiological aspects ,Science and technology - Abstract
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. antiviral response | coxsackievirus | cytokine | IFN-[gamma] | Toll-like receptor 3
- Published
- 2008