@article{6e39ec5ad9284ae1b859ec2f1111e197,
title = "IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP",
abstract = "Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels. Depletion of IFI16 in macrophages impairs cGAMP production on DNA stimulation, whereas overexpression of IFI16 amplifies the function of cGAS. Furthermore, IFI16 is vital for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-binding kinase 1 in STING complex. Collectively, our results suggest that IFI16 is essential for efficient sensing and signalling upon DNA challenge in macrophages to promote interferons and antiviral responses.",
author = "J{\o}nsson, {K. L.} and A. Laustsen and C. Krapp and Skipper, {K. A.} and K. Thavachelvam and D. Hotter and Egedal, {J. H.} and M. Kjolby and P. Mohammadi and T. Prabakaran and S{\o}rensen, {L. K.} and C. Sun and Jensen, {S. B.} and Holm, {C. K.} and Lebbink, {R. J.} and M. Johannsen and M. Nyegaard and Mikkelsen, {J. G.} and F. Kirchhoff and Paludan, {S. R.} and Jakobsen, {M. R.}",
note = "Funding Information: This work was primarily supported by grants (for M.R.J. and K.L.J.) from Danish Council for Independent Research (4004-00237), The Lundbeck Foundation (R151-2013-14443), Augustinus Fond, Aarhus University Research Foundation and Frode V. Nyegaard og Hustrus Fond. Additional grant supported for S.R.P.: The Danish Medical Research Council (12-124330), The Novo Nordisk Foundation, The Lundbeck Foundation (R198-2015-171) and The Chinese Scholarship Council (for S.C. fellowship); for J.G.M.: Danish Council for Independent Research (4004-00220); for F.K.: The Deutsche Forschungsgemeinschaft, European FP7 'HIT HIDDEN HIV' (305762), a Leibniz award of the Deutsche Forschungsgemeinschaft, and Advanced ERC investigator grant; for D.H.: The International Graduate school in Molecular Medicine Ulm; for R.J.L.: Veni grant 916.10.138 from The Netherlands Organisation for Scientific Research (NWO) and Dutch Cancer Society grant UU 2012-5667. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
month = feb,
day = "10",
doi = "10.1038/ncomms14391",
language = "English (US)",
volume = "8",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}