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

Almine, Jessica F.; O’Hare, Craig A.J.; Dunphy, Gillian; Haga, Ismar R.; Naik, Rangeetha J.; Atrih, Abdelmadjid; Connolly, Dympna J.; Taylor, Jordan; Kelsall, Ian R.; Bowie, Andrew G.; Beard, Philippa M.; Unterholzner, Leonie

Abstract

<jats:title>Abstract</jats:title><jats:p>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-? 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.</jats:p>

Citation

Almine, J. F., O’Hare, C. A., Dunphy, G., Haga, I. R., Naik, R. J., Atrih, A., …Unterholzner, L. (2017). IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nature communications, 8, Article 14392. https://doi.org/10.1038/ncomms14392

• Journal Article Type: Article
• Acceptance Date: Dec 22, 2016
• Publication Date: Feb 13, 2017
• Journal: Nature Communications
• Print ISSN: 2041-1723
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Article Number: 14392
• DOI: https://doi.org/10.1038/ncomms14392
• Publisher URL: https://www.nature.com/articles/ncomms14392