IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes

Almine, Jessica F. and O'Hare, Craig A. J. and Dunphy, Gillian and Haga, Ismar R. and Naik, Rangeetha J. and Atrih, Abdelmadjid and Connolly, Dympna J. and Taylor, Jordan and Kelsall, Ian R. and Bowie, Andrew G. and Beard, Philippa M. and Unterholzner, Leonie (2017) IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nature Communications, 8. ISSN 2041-1723

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Nature Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3100
Subjects:
ID Code:
84952
Deposited By:
Deposited On:
28 Feb 2017 13:56
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Dec 2020 04:26