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Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis.

Authors :
Domínguez-Andrés, Jorge
Arts, Rob J. W.
ter Horst, Rob
Gresnigt, Mark S.
Smeekens, Sanne P.
Ratter, Jacqueline M.
Lachmandas, Ekta
Boutens, Lily
van de Veerdonk, Frank L.
Joosten, Leo A. B.
Notebaart, Richard A.
Ardavín, Carlos
Netea, Mihai G.
Source :
PLoS Pathogens. 9/18/2017, Vol. 13 Issue 9, p1-23. 23p.
Publication Year :
2017

Abstract

Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15537366
Volume :
13
Issue :
9
Database :
Academic Search Index
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
125204687
Full Text :
https://doi.org/10.1371/journal.ppat.1006632