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

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

研究成果: Article査読

165 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)20446-20451
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
105
51
DOI
出版ステータスPublished - 2008 12月 23
外部発表はい

ASJC Scopus subject areas

  • 一般

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