Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function.

中文翻译：

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细胞固有的糖原代谢支持树突状细胞免疫反应所需的早期糖酵解重编程。

Toll样受体（TLR）激动剂对树突状细胞（DC）的激活引起快速的糖酵解重编程，这是满足其免疫激活的代谢要求所必需的。在该领域的最新努力已经确定了细胞外葡萄糖来源以支持DC活化的重要作用。但是，细胞内葡萄糖储存对这些过程的贡献尚未得到很好的表征。我们证明DC具有细胞内糖原存储，并且细胞内糖原代谢支持TLR激活的DC的早期效应功能。糖原分解的抑制作用显着减弱了TLR介导的DC成熟，并削弱了其启动淋巴细胞活化的能力。我们进一步报告说，DC表现出葡萄糖和糖原衍生碳的功能区室化，这些底物优先促成独特的代谢途径。这项工作提供了DC中营养稳态的新颖见解，证明了糖原和葡萄糖代谢的差异利用调节了它们的最佳免疫功能。