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

• Published in: PLoS pathogens Vol. 13; no. 9; p. e1006632
• Main 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.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2017; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Biology and Life Sciences; Candida; Candida albicans; Candidiasis; Candidiasis - metabolism; Cell activation; Food Microbiology; Food Microbiology Laboratory; Funding; Fungal diseases; Fungal infections; Fungi; Fungicides; Gene expression; Genomics; Glucose; Glucose - metabolism; Glycolysis; Glycolysis - drug effects; Grants; Humans; Hyphae; Immune response; Immune system; Immunity; Immunity, Innate - immunology; Immunology; Infections; Infectious diseases; Innate immunity; Internal medicine; Internet; Laboratories; Laboratorium Levensmiddelenmicrobiologie; Lectins; Lectins, C-Type - metabolism; Levensmiddelenmicrobiologie; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Mice; Monocytes; Monocytes - metabolism; Oxidative metabolism; Oxidative phosphorylation; Phosphorylation; Research and Analysis Methods; Signal Transduction; Supervision; Yeast; Netherlands
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006632

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.