Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1β production to β-glucan ligands in a TLR-independent manner

[摘要] Dendritic cells (DCs) activated via TLR ligation experience metabolic reprogramming, in which the cells are heavily dependent on glucose and glycolysis for the synthesis of molecular building blocks essential for maturation, cytokine production, and the ability to stimulate T cells. Although the TLR-driven metabolic reprogramming events are well documented, fungal-mediated metabolic regulation via C-type lectin receptors such as Dectin-1 and Dectin-2 is not clearly understood. Here, we show that activation of DCs with fungal-associated ?-glucan ligands induces acute glycolytic reprogramming that supports the production of IL-1? and its secretion subsequent to NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. This acute glycolytic induction in response to ?-glucan ligands requires spleen tyrosine kinase signaling in a TLR-independent manner, suggesting now that different classes of innate immune receptors functionally induce conserved metabolic responses to support immune cell activation. These studies provide new insight into the complexities of metabolic regulation of DCs immune effector function regarding cellular activation associated with protection against fungal microbes.

[学科分类] 生理学

[关键词] dectin-1/2;dendritic cells (DCs);glycolysis;inflammasome;NOD-;LRR- and pyrin domaincontaining protein 3 (NLRP3);oxidative phosphorylation (OXPHOS);pattern recognition receptor (PRR);spleen tyrosine kinase (Syk);toll-like receptor (TLR)