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

PLoS Pathogens

Rob J. W. Arts¹  Mihai G. Netea¹  Frank L. van de Veerdonk²  Rob ter Horst²  Leo A. B. Joosten²  Mark S. Gresnigt²  Jacqueline M. Ratter²  Richard A. Notebaart²  Lily Boutens²  Jorge Domínguez-Andrés²  Sanne P. Smeekens²  Ekta Lachmandas²  Carlos Ardavín³ 

[1] Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Darwin 3, Madrid, Spain;Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, Nijmegen, the Netherlands;Laboratory of Food Microbiology, Wageningen University and Research, Wageningen, The Netherlands

关键词: C;    ida albicans;    Monocytes;    Glycolysis;    Glucose metabolism;    Cytokines;    Yeast infections;    Cell metabolism;    Yeast;   

DOI  :  10.1371/journal.ppat.1006632

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY