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

• DOI: 10.1371/journal.ppat.1006632
• Publication Date: 2017-09-18T19:27:23Z
• Authors: Jorge Domínguez-A...; Rob J. W. Arts; Rob ter Horst; Mark S. Gresnigt; Sanne P. Smeekens; Jacqueline M. Ratter; Ekta Lachmandas; Lily Boutens; Frank L. van de V...; Leo A. B. Joosten; Richard A. Notebaart; Carlos Ardavín; Mihai G. Netea
• Keywords: Glutaminolysis; Metabolic pathway; Monocyte; Carbohydrate Metabolism

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