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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Phyu M. Thwe¹  Daniel I. Fritz¹  Julia P. Snyder¹  Portia R. Smith¹  Kylie D. Curtis¹  Alexandra O'Donnell¹  Nicholas A. Galasso¹  Leslie A. Sepaniac¹  Benjamin J. Adamik¹  Laura R. Hoyt¹  Princess D. Rodriguez¹  Tyler C. Hogan¹  Andrea F. Schmidt¹  Matthew E. Poynter²  Eyal Amiel³ 

[1] and Biomedical (CMB) Sciences Graduate Program, University of Vermont;Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont;Department of Biomedical and Health Sciences, University of Vermont

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);   

DOI  :  10.1002/JLB.3A0819-207RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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.

【 授权许可】

CC BY