Department of Immunology, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nat Immunol. 2011 Sep 4;12(10):959-65. doi: 10.1038/ni.2091.
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.
对病原 DNA 的识别对启动抗病毒反应很重要。在这里，我们报告了 DDX41 的鉴定，它是 DEXXDc 家族解旋酶的一个成员，作为髓样树突状细胞 (mDCs) 中的一种细胞内 DNA 传感器。短发夹 RNA 敲低 DDX41 的表达阻断了 mDCs 对 DNA 和 DNA 病毒产生 I 型干扰素和细胞因子反应的能力。DDX41 和膜相关衔接蛋白 STING 的过表达在促进 Ifnb 启动子活性方面具有协同作用。DDX41 与 DNA 和 STING 结合，并与 STING 一起在细胞质中定位。DDX41 表达的敲低阻断了 B 型 DNA 对丝裂原活化蛋白激酶 TBK1 和转录因子 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 来感知病原 DNA。
