IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes.
IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes.
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DOI：
10.1038/ncomms14392
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发表时间：
2017-02-13
影响因子：
16.6
通讯作者：
Unterholzner L
中科院分区：
文献类型：
--
作者：
Almine JF;O'Hare CA;Dunphy G;Haga IR;Naik RJ;Atrih A;Connolly DJ;Taylor J;Kelsall IR;Bowie AG;Beard PM;Unterholzner L
许多人类细胞可以通过胞质DNA受体环GMP-AMP合酶（cGAS）在感染期间感知外源DNA的存在，所述cGAS产生第二信使环GMP-AMP（cGAMP）。已经描述了其他推定的DNA受体，但它们的功能是否是冗余的、组织特异性的或整合在cGAS-cGAMP途径中尚不清楚。在这里，我们表明干扰素-γ诱导蛋白16（IFI 16）在人角质形成细胞中的DNA传感期间与cGAS合作，因为cGAS和IFI 16都是完全激活对外源DNA和DNA病毒的先天免疫应答所必需的。IFI 16也是cGAMP诱导的STING活化所必需的，并与STING相互作用以促进STING磷酸化和易位。我们建议两个DNA传感器IFI 16和cGAS合作，以防止假激活的I型干扰素反应。IFI 16作为DNA传感器的作用是非常有争议的。在Jønsson等人的《自然通讯》背靠背出版物的支持下，作者在此提供了IFI 16通过人角质形成细胞中的cGAS-STING途径参与DNA传感的功能证据。
Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response. The role of IFI16 as a DNA sensor is highly controversial. With support from a Nature Communications back-to-back publication from Jønsson et al., the authors here provide functional evidence that IFI16 is involved in DNA sensing via the cGAS-STING pathway in human keratinocytes.