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

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141 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20446-20451
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number51
DOIs
Publication statusPublished - 2008 Dec 23

Keywords

  • Antiviral response
  • Coxsackievirus
  • Cytokine
  • IFN-γ
  • Toll-like receptor 3

ASJC Scopus subject areas

  • General

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    Negishi, H., Osawa, T., Ogami, K., Ouyang, X., Sakaguchi, S., Koshiba, R., Yanai, H., Seko, Y., Shitara, H., Bishop, K., Yonekawa, H., Tamura, T., Kaisho, T., Taya, C., Taniguchi, T., & Honda, K. (2008). A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America, 105(51), 20446-20451. https://doi.org/10.1073/pnas.0810372105