The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells.

The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells.
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DOI:
10.1038/ni.2091
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发表时间:
2011-09-04
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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对致病DNA的识别对于启动抗病毒反应是很重要的。在这里,我们报告了作为髓系树突状细胞(MDCS)细胞内DNA感受器的DDX41,它是DEXDc解旋酶家族的成员。通过短发夹状RNA抑制DDX41的表达,阻断了MDCS对DNA和DNA病毒的I型干扰素和细胞因子反应。DDX41的过表达和膜相关接头结合在一起,在促进Ifnb启动子活性方面具有协同作用。DDX41与DNA和STING结合,并与STING一起定位在胞浆中。抑制DDX41的表达可阻断B型DNA对丝裂原活化蛋白激酶Tbk1、转录因子NF-κB和IRF3的激活。我们的结果表明,DDX41是一种额外的DNA传感器,它依赖于STING来感知致病DNA。
The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here we report the identification of DDX41, a member of the DEXDc family of helicases, as an intracellular DNA sensor in myeloid dendritic cells (mDCs). Knockdown of DDX41 expression by short hairpin RNA blocked the ability of mDCs to mount type I interferon and cytokine responses to DNA and DNA viruses. Overexpression of both DDX41 and the membrane-associated adaptor STING together had a synergistic effect in promoting Ifnb promoter activity. DDX41 bound both DNA and STING and localized together with STING in the cytosol. Knockdown of DDX41 expression blocked activation of the mitogen-activated protein kinase TBK1 and the transcription factors NF-κB and IRF3 by B-form DNA. Our results suggest that DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA.
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