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

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^*

来源：Nature Immunology, 2006, 7(1): 40-48.

DOI：10.1038/ni1282

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.

• 出版日期2006-1