TY - JOUR
T1 - A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity
AU - Negishi, Hideo
AU - Osawa, Tomoko
AU - Ogami, Kentaro
AU - Ouyang, Xinshou
AU - Sakaguchi, Shinya
AU - Koshiba, Ryuji
AU - Yanai, Hideyuki
AU - Seko, Yoshinori
AU - Shitara, Hiroshi
AU - Bishop, Keith
AU - Yonekawa, Hiromichi
AU - Tamura, Tomohiko
AU - Kaisho, Tsuneyasu
AU - Taya, Choji
AU - Taniguchi, Tadatsugu
AU - Honda, Kenya
PY - 2008/12/23
Y1 - 2008/12/23
N2 - 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.
AB - 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.
KW - Antiviral response
KW - Coxsackievirus
KW - Cytokine
KW - IFN-γ
KW - Toll-like receptor 3
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U2 - 10.1073/pnas.0810372105
DO - 10.1073/pnas.0810372105
M3 - Article
C2 - 19074283
AN - SCOPUS:58149510024
SN - 0027-8424
VL - 105
SP - 20446
EP - 20451
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
ER -