Monocytes –innate immune system cells of great importance in the defence against fungal infections– modify their metabolism according to energy requirements to combat the different forms of the fungus Candida albicans. This is the conclusion reached by researchers from the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC) in collaboration with scientists in other European institutions and published in the journal PLoS Pathogens. The study is the result of collaboration between Mihai Netea's laboratory at the Radboud University Nijmegen (the Netherlands) and Carlos Ardavín at the CNB-CSIC.
Several routes of monocyte glucose metabolism –specifically glycolysis, oxidative phosphorylation and the pentose phosphate cycle– are affected by a Candida infection depending on whether it is in the form of yeast or hyphae. "We observed that the control of cell metabolism is fundamental in the response to the different C. albicans forms. Modulating the metabolic processes in immune cells through drugs could be a new therapeutic strategy against fungal infections," explains Jorge Domínguez, a CNB-CSIC researcher and a co-author of the study.
The main pathogenic fungus in humans
Although fungal infections pose a major threat, their impact on human health is not as well-recognized as that of other diseases. It is estimated that systemic candidiasis affects half a million individuals each year. It is a problem of special importance for immunosuppressed patients, among whom causes up to 40% mortality.
The limited effectiveness of existing pharmacological therapies and the emergence of new multi-resistant Candida species lead to increasingly severe infections. "It is urgent to promote basic research in this field and explore new antifungal therapeutic strategies," says Domínguez.
Referencia: Domínguez-Andrés J, Arts RJW, Ter Horst R, Gresnigt MS, Smeekens SP, Ratter JM, Lachmandas E, Boutens L, van de Veerdonk FL, Joosten LAB, Notebaart RA, Ardavín C, Netea MG. Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. PLoS Pathog. 2017 Sep 18;13(9):e1006632. doi: 10.1371/journal.ppat.1006632