Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells.

细胞代谢是免疫细胞功能的基础，但我们对人类树突状细胞生物学中代谢影响及其协调免疫反应能力的理解尚不完善。在这里，我们使用最近开发的多参数方法绘制了炎症和耐受性单核细胞树突状细胞的单细胞代谢状态和免疫谱。单细胞代谢途径激活评分揭示了多种代谢途径同时参与不同的单核细胞树突细胞分化阶段。GM-CSF/IL4-诱导糖酵解单核细胞的快速重编程和线粒体途径的瞬时共激活，随后树突状细胞的 TLR4 依赖性成熟。mTOR 的倾斜：AMPK 磷酸化平衡和 OXPHOS 的上调，糖酵解和脂肪酸氧化代谢是代谢过度活跃和耐受性树突状细胞免疫抑制表型的基础，树突状细胞表现出成熟抗性和以独特免疫调节受体特征为标志的去分化免疫表型。这个单细胞数据集提供了对影响人类树突状细胞免疫谱的代谢途径的重要见解。