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IRF7 Exacerbates Candida albicans Infection by Compromising CD209-Mediated Phagocytosis and Autophagy-Mediated Killing in Macrophages.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Jun 15; Vol. 212 (12), pp. 1932-1944. - Publication Year :
- 2024
-
Abstract
- IFN regulatory factor 7 (IRF7) exerts anti-infective effects by promoting the production of IFNs in various bacterial and viral infections, but its role in highly morbid and fatal Candida albicans infections is unknown. We unexpectedly found that Irf7 gene expression levels were significantly upregulated in tissues or cells after C. albicans infection in humans and mice and that IRF7 actually exacerbates C. albicans infection in mice independent of its classical function in inducing IFNs production. Compared to controls, Irf7-/- mice showed stronger phagocytosis of fungus, upregulation of C-type lectin receptor CD209 expression, and enhanced P53-AMPK-mTOR-mediated autophagic signaling in macrophages after C. albicans infection. The administration of the CD209-neutralizing Ab significantly hindered the phagocytosis of Irf7-/- mouse macrophages, whereas the inhibition of p53 or autophagy impaired the killing function of these macrophages. Thus, IRF7 exacerbates C. albicans infection by compromising the phagocytosis and killing capacity of macrophages via regulating CD209 expression and p53-AMPK-mTOR-mediated autophagy, respectively. This finding reveals a novel function of IRF7 independent of its canonical IFNs production and its unexpected role in enhancing fungal infections, thus providing more specific and effective targets for antifungal therapy.<br /> (Copyright © 2024 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Mice
Humans
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Protein p53 genetics
Mice, Inbred C57BL
Cell Adhesion Molecules genetics
Cell Adhesion Molecules metabolism
Signal Transduction immunology
Phagocytosis immunology
Autophagy immunology
Lectins, C-Type genetics
Lectins, C-Type metabolism
Candidiasis immunology
Candida albicans immunology
Candida albicans physiology
Interferon Regulatory Factor-7 genetics
Interferon Regulatory Factor-7 metabolism
Interferon Regulatory Factor-7 immunology
Macrophages immunology
Mice, Knockout
Receptors, Cell Surface genetics
Receptors, Cell Surface metabolism
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 212
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 38709167
- Full Text :
- https://doi.org/10.4049/jimmunol.2300826