IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP

K. L. Jønsson, A. Laustsen, C. Krapp, K. A. Skipper, K. Thavachelvam, D. Hotter, J. H. Egedal, M. Kjolby, P. Mohammadi, T. Prabakaran, L. K. Sørensen, C. Sun, S. B. Jensen, C. K. Holm, R. J. Lebbink, M. Johannsen, M. Nyegaard, J. G. Mikkelsen, F. Kirchhoff, S. R. Paludan and M. R. Jakobsen ()
Additional contact information
K. L. Jønsson: Aarhus University
A. Laustsen: Aarhus University
C. Krapp: Aarhus University
K. A. Skipper: Aarhus University
K. Thavachelvam: Aarhus University
D. Hotter: Ulm University Medical Center, Institute of Molecular Virology
J. H. Egedal: Aarhus University
M. Kjolby: Aarhus University
P. Mohammadi: New York Genome Center
T. Prabakaran: Aarhus University
L. K. Sørensen: Aarhus University Hospital
C. Sun: Aarhus University
S. B. Jensen: Aarhus University
C. K. Holm: Aarhus University
R. J. Lebbink: University Medical Center Utrecht
M. Johannsen: Aarhus University Hospital
M. Nyegaard: Aarhus University
J. G. Mikkelsen: Aarhus University
F. Kirchhoff: Ulm University Medical Center, Institute of Molecular Virology
S. R. Paludan: Aarhus University
M. R. Jakobsen: Aarhus University

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms14391 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14391

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14391

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().