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The transcription factor IRF3 triggers "defensive suicide" necrosis in response to viral and bacterial pathogens.
- Source :
-
Cell reports [Cell Rep] 2013 Jun 27; Vol. 3 (6), pp. 1840-6. Date of Electronic Publication: 2013 Jun 13. - Publication Year :
- 2013
-
Abstract
- Although molecular components that execute noninflammatory apoptotic cell death are well defined, molecular pathways that trigger necrotic cell death remain poorly characterized. Here, we show that in response to infection with adenovirus or Listeria monocytogenes, macrophages in vivo undergo rapid proinflammatory necrotic death that is controlled by interferon-regulatory factor 3 (IRF3). The transcriptional activity of IRF3 is, surprisingly, not required for the induction of necrosis, and it proceeds normally in mice deficient in all known regulators of necrotic death or IRF3 activation, including RIPK3, caspases 1, 8, or 11, STING, and IPS1/MAVS. Although L. monocytogenes triggers necrosis to promote the infection, IRF3-dependent necrosis is required for reducing pathogen burden in the models of disseminated infection with adenovirus. Therefore, our studies implicate IRF3 as a principal and nonredundant component of a physiologically regulated necrotic cell-death pathway that operates as an effective innate immune mechanism of host protection against disseminated virus infection.<br /> (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adenovirus Infections, Human pathology
Animals
Caspases metabolism
Immunity, Innate immunology
Interferon Regulatory Factor-3 deficiency
Interferon Regulatory Factor-3 genetics
Listeriosis pathology
Macrophages immunology
Macrophages virology
Mice
Mice, Inbred C57BL
Mice, Knockout
Necrosis immunology
Necrosis pathology
Receptor-Interacting Protein Serine-Threonine Kinases metabolism
Signal Transduction
Adenovirus Infections, Human immunology
Adenoviruses, Human immunology
Interferon Regulatory Factor-3 immunology
Listeria monocytogenes immunology
Listeriosis immunology
Macrophages microbiology
Macrophages pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 3
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 23770239
- Full Text :
- https://doi.org/10.1016/j.celrep.2013.05.025