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.
Highlights
The immune system is constantly challenged by pathogens, and this requires immune cells to optimize the management of metabolic resources in order to exert their crucial role in host defense
We describe how changes in monocyte glucose metabolism are crucial for host defense against infections caused by the opportunistic pathogenic yeast Candida albicans
We validated the upregulation observed in those genes by qPCR in monocytes isolated from healthy volunteers stimulated with heat-killed yeast or hyphae for 24 h finding a significant upregulation of some of the main enzymes involved in glycolysis such as hexokinase (HK) and phosphofructokinase (PFKP)
Summary
The immune system is constantly challenged by pathogens, and this requires immune cells to optimize the management of metabolic resources in order to exert their crucial role in host defense. A number of studies have shown how different stimuli induce metabolic reprogramming in immune cells, required for the response against microbial infections [1,2,3]. Recent studies led to the understanding that the differential use of carbon and nitrogen sources can subsequently affect the immune response. In this sense, proinflammatory macrophages and neutrophils favor aerobic glycolysis over oxidative phosphorylation [4], anti-inflammatory macrophages rely more on fatty acid oxidation and TCA cycle [5], whereas full T cell activation requires the induction of mitochondrial ROS [6]. Monocytes have been shown to play a crucial role against C. albicans infection, as the deficiency in this immune cell subset has been related with higher susceptibility to fungal infections both in mice and humans [11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
