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Nat Commun. 2017 Feb 13;8:14392. doi: 10.1038/ncomms14392.

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

Author information

1
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
2
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
3
The Pirbright Institute, Pirbright, Surrey GU24 0NF, UK.
4
Fingerprints Proteomics Facility, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
5
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
6
The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.

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.

PMID:
28194029
PMCID:
PMC5316833
DOI:
10.1038/ncomms14392
[Indexed for MEDLINE]
Free PMC Article

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