Immune cells modify their metabolic pathways in response to fungal infections. Nevertheless, the biochemical underpinnings need to be better understood. This study reports that fungal infection drives a switch from glycolysis to the serine synthesis pathway (SSP) and one-carbon metabolism by inducing the interaction of spleen tyrosine kinase (SYK) and phosphoglycerate dehydrogenase (PHGDH). As a result, PHGDH promotes SYK phosphorylation, leading to the recruitment of SYK to C-type lectin receptors (CLRs). The CLR/SYK complex initiates signaling cascades that lead to transcription factor activation and pro-inflammatory cytokine production. SYK activates SSP and one-carbon metabolism by inducing PHGDH activity. Then, one-carbon metabolism supports S-adenosylmethionine and histone H3 lysine 36 trimethylation to drive the production of pro-inflammatory cytokines and chemokines. These findings reveal the crosstalk between amino acid metabolism, epigenetic modification, and CLR signaling during fungal infection.

免疫细胞改变其代谢途径以应对真菌感染。然而，我们还需要更好地理解其生化基础。这项研究报告称，真菌感染通过诱导脾酪氨酸激酶（SYK）和磷酸甘油酸脱氢酶（PHGDH）的相互作用，驱动从糖酵解到丝氨酸合成途径（SSP）和一碳代谢的转变。结果，PHGDH 促进 SYK 磷酸化，导致 SYK 募集到 C 型凝集素受体 (CLR)。 CLR/SYK 复合物启动信号级联，导致转录因子激活和促炎细胞因子产生。 SYK 通过诱导 PHGDH 活性来激活 SSP 和一碳代谢。然后，一碳代谢支持 S-腺苷甲硫氨酸和组蛋白 H3 赖氨酸 36 三甲基化，以驱动促炎细胞因子和趋化因子的产生。这些发现揭示了真菌感染过程中氨基酸代谢、表观遗传修饰和 CLR 信号传导之间的串扰。