Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes
AU - Almine, Jessica F.
AU - O'Hare, Craig A. J.
AU - Dunphy, Gillian
AU - Haga, Ismar R.
AU - Naik, Rangeetha J.
AU - Atrih, Abdelmadjid
AU - Connolly, Dympna J.
AU - Taylor, Jordan
AU - Kelsall, Ian R.
AU - Bowie, Andrew G.
AU - Beard, Philippa M.
AU - Unterholzner, Leonie
PY - 2017/2/13
Y1 - 2017/2/13
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms14392
DO - 10.1038/ncomms14392
M3 - Journal article
C2 - 28194029
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 14392
ER -