IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP
| Autor: | Jacob Giehm Mikkelsen, Mogens Johannsen, Mette Nyegaard, Anders Laustsen, Chenglong Sun, Mads Kjolby, Pejman Mohammadi, Martin R. Jakobsen, Dominik Hotter, Thaneas Prabakaran, Søren R. Paludan, Lambert K. Sørensen, Kristian Alsbjerg Skipper, Johanne H Egedal, Karthiga Thavachelvam, Kasper L Jønsson, Frank Kirchhoff, Søren B. Jensen, Christian K. Holm, Christian Krapp, Robert Jan Lebbink |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
STING complex Microbial DNA THP-1 Cells Science General Physics and Astronomy Biology Protein Serine-Threonine Kinases medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine RNA interference medicine Journal Article Humans Cells Cultured health care economics and organizations Mutation Multidisciplinary Innate immune system IFI16 Gene Expression Profiling Macrophages Membrane Proteins Nuclear Proteins General Chemistry DNA Phosphoproteins equipment and supplies Nucleotidyltransferases Immunity Innate Cell biology 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Stimulator of interferon genes RNA Interference Interferons Signal transduction Nucleotides Cyclic human activities Signal Transduction |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-17 (2017) Jønsson, K L, Laustsen, A, Krapp, C, Skipper, K A, Thavachelvam, K, Hotter, D, Egedal, J H, Kjolby, M, Mohammadi, P, Prabakaran, T, Sørensen, L K, Sun, C, Jensen, S B, Holm, C K, Lebbink, R J, Johannsen, M, Nyegaard, M, Mikkelsen, J G, Kirchhoff, F, Paludan, S R & Jakobsen, M R 2017, ' IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP ', Nature Communications, vol. 8, 14391 . https://doi.org/10.1038/ncomms14391 Nature Communications Nature Communications [E], 8. Nature Publishing Group |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms14391 |
| Popis: | 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. The role of IFI16 as a DNA sensor is highly controversial. With support from a Nature Communications back-to-back publication from Almine et al. the authors here provide functional evidence that IFI16 is required for DNA sensing via the cGAS-STING pathway in human macrophages. |
| Databáze: | OpenAIRE |
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