DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells.

DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells.
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DOI:
10.4049/jimmunol.1101307
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发表时间:
2011-11-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Liu YJ
Liu YJ
中科院分区:
其他
文献类型:
--
作者:
Zhang Z;Yuan B;Lu N;Facchinetti V;Liu YJ

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先天免疫系统配备有许多微生物DNA/RNA的分子传感器,以快速启动抗微生物宿主免疫应答。在本文中,我们确定DHX 9,DExDc解旋酶家族成员,作为一个重要的病毒dsRNA传感器在髓样树突状细胞(mDC)。通过小异源双链RNA敲低DHX 9表达显著阻断了mDC产生IFN-α/β和促炎细胞因子以响应聚肌苷-聚胞苷酸、甲型流感和呼肠孤病毒的能力。DHX 9可通过其双链RNA结合基序特异性结合聚肌苷-聚胞苷酸。DHX 9分别通过DHX 9和IPS-1的HelicC-HA 2-DUF和CARD结构域与IPS-1相互作用。下调DHX 9表达可阻断dsRNA对NF-κB和IFN调节因子3的激活。总的来说,这些结果表明DHX 9是一种重要的RNA传感器,它依赖于IPS-1来感测致病性RNA。
The innate immune system is equipped with many molecular sensors for microbial DNA/RNA to quickly mount antimicrobial host immune responses. In this paper, we identified DHX9, a DExDc helicase family member, as an important viral dsRNA sensor in myeloid dendritic cells (mDCs). Knockdown of DHX9 expression by small heteroduplex RNA dramatically blocked the ability of mDCs to produce IFN-α/β and proinflammatory cytokines in response to polyinosine-polycytidylic acid, influenza A, and reovirus. DHX9 could specifically bind polyinosine-polycytidylic acid via its double-strand RNA binding motifs. DHX9 interacted with IPS-1 via the HelicC-HA2-DUF and CARD domains of DHX9 and IPS-1, respectively. Knockdown of DHX9 expression in mDCs blocked the activation of NF-κB and IFN regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA.
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