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.

单核细胞是在抗真菌免疫中起关键作用的先天免疫细胞，但对于在感染过程中调节其功能的细胞代谢事件知之甚少。使用在人类原代单核细胞中进行的补充转录组学和免疫学研究，我们表明由白色念珠菌酵母菌丝和菌丝激活单核细胞伴随着通过C型凝集素信号通路诱导的新陈代谢。我们描述了针对念珠菌的先天免疫反应酵母是需要能量的过程，导致细胞内代谢物库的动员，需要诱导葡萄糖代谢，氧化磷酸化和谷氨酰胺分解，而对菌丝的反应主要依赖于糖酵解。系统性念珠菌病模型的实验模型验证了糖代谢在抗念珠菌免疫中的核心作用，因为糖酵解的损伤导致小鼠易感性增加。这些数据共同强调了了解感染期间触发的复杂代谢反应网络的重要性，并揭示了针对真菌疾病的治疗方法的新潜在目标。