A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA

被引:628
作者
Ishii, KJ
Coban, C
Kato, H
Takahashi, K
Torii, Y
Takeshita, F
Ludwig, H
Sutter, G
Suzuki, K
Hemmi, H
Sato, S
Yamamoto, M
Uematsu, S
Kawai, T
Takeuchi, O
Akira, S
机构
[1] Osaka Univ, Exploratory Res Adv Technol, Japan Sci & Technol Agcy, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Dept Host Def, Suita, Osaka 5650871, Japan
[3] Osaka Univ, 21 Century COE, Combined Program Microbiol & Immunol, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan
[4] Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 2360004, Japan
[5] Paul Ehrlich Inst, Abt Virol, D-63225 Langen, Germany
[6] Natl Inst Infect Dis, Leprosy Res Ctr, Dept Host Def, Tokyo 1890002, Japan
关键词
D O I
10.1038/ni1282
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The innate immune system recognizes nucleic acids during infection or tissue damage; however, the mechanisms of intracellular recognition of DNA have not been fully elucidated. Here we show that intracellular administration of double-stranded B-form DNA (B-DNA) triggered antiviral responses including production of type I interferons and chemokines independently of Toll-like receptors or the helicase RIG-I. B-DNA activated transcription factor IRF3 and the promoter of the gene encoding interferon-beta through a signaling pathway that required the kinases TBK1 and IKKi, whereas there was substantial activation of transcription factor NF-kappa B independent of both TBK and IKKi. IPS-1, an adaptor molecule linking RIG-I and TBK1, was involved in B-DNA-induced activation of interferon-beta and NF-kappa B. B-DNA signaling by this pathway conferred resistance to viral infection in a way dependent on both TBK1 and IKKi. These results suggest that both TBK1 and IKKi are required for innate immune activation by B-DNA, which might be important in antiviral innate immunity and other DNA-associated immune disorders.
引用
收藏
页码:40 / 48
页数:9
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