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

Jessica F. Almine, Craig A. J. O’Hare, Gillian Dunphy, Ismar R. Haga, Rangeetha J. Naik, Abdelmadjid Atrih, Dympna J. Connolly, Jordan Taylor, Ian R. Kelsall, Andrew G. Bowie, Philippa M. Beard and Leonie Unterholzner ()
Additional contact information
Jessica F. Almine: School of Life Sciences, University of Dundee
Craig A. J. O’Hare: School of Life Sciences, University of Dundee
Gillian Dunphy: School of Life Sciences, University of Dundee
Ismar R. Haga: The Pirbright Institute
Rangeetha J. Naik: School of Life Sciences, University of Dundee
Abdelmadjid Atrih: Fingerprints Proteomics Facility, School of Life Sciences, University of Dundee
Dympna J. Connolly: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin
Jordan Taylor: School of Life Sciences, University of Dundee
Ian R. Kelsall: School of Life Sciences, University of Dundee
Andrew G. Bowie: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin
Philippa M. Beard: The Pirbright Institute
Leonie Unterholzner: School of Life Sciences, University of Dundee

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14392

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