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

Author

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  • Jessica F. Almine

    (School of Life Sciences, University of Dundee
    Faculty of Health and Medicine, Lancaster University)

  • Craig A. J. O’Hare

    (School of Life Sciences, University of Dundee
    Faculty of Health and Medicine, Lancaster University)

  • Gillian Dunphy

    (School of Life Sciences, University of Dundee
    Faculty of Health and Medicine, Lancaster University)

  • 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
    The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh)

  • Leonie Unterholzner

    (School of Life Sciences, University of Dundee
    Faculty of Health and Medicine, Lancaster University)

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.

Suggested Citation

  • 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. Be, 2017. "IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14392
    DOI: 10.1038/ncomms14392
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    Cited by:

    1. Qin Yan & Jing Zhou & Ziyu Wang & Xiangya Ding & Xinyue Ma & Wan Li & Xuemei Jia & Shou-Jiang Gao & Chun Lu, 2023. "NAT10-dependent N4‐acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Martha Triantafilou & Joshi Ramanjulu & Lee M. Booty & Gisela Jimenez-Duran & Hakan Keles & Ken Saunders & Neysa Nevins & Emma Koppe & Louise K. Modis & G. Scott Pesiridis & John Bertin & Kathy Triant, 2022. "Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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