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

Jorge Domínguez-Andrés*, Rob J.W. Arts, Rob ter Horst, Mark S. Gresnigt, Sanne P. Smeekens, Jacqueline M. Ratter, Ekta Lachmandas, Lily Boutens, Frank L. van de Veerdonk, Leo A.B. Joosten, Richard A. Notebaart, Carlos Ardavín, Mihai G. Netea

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Article numbere1006632
Number of pages23
JournalPLoS Pathogens
Volume13
Issue number9
DOIs
Publication statusPublished - 18 Sep 2017

Fingerprint Dive into the research topics of 'Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis'. Together they form a unique fingerprint.

Cite this