A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA
A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA
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DOI：
10.1038/ni1282
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发表时间：
2006-01-01
影响因子：
30.5
通讯作者：
Akira, S
中科院分区：
文献类型：
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作者：
Ishii, KJ;Coban, C;Akira, S
先天免疫系统在感染或组织损伤时识别核酸；然而，细胞内DNA识别的机制尚未完全阐明。本研究表明，细胞内给予双链b型DNA （B-DNA）可触发抗病毒反应，包括独立于toll样受体或解旋酶rig - 1的I型干扰素和趋化因子的产生。B- dna通过需要TBK1和IKKi激酶的信号通路激活转录因子IRF3和编码干扰素- β的基因启动子，而转录因子NF-kappa B的大量激活独立于TBK和IKKi。连接rig -1和TBK1的接头分子IPS-1参与了B-DNA诱导的干扰素- β和NF-kappa b的激活，B-DNA信号通过该途径以依赖TBK1和IKKi的方式赋予病毒感染的抗性。这些结果表明TBK1和IKKi都是B-DNA激活先天免疫所必需的，这可能在抗病毒先天免疫和其他dna相关免疫疾病中很重要。
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.