Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses

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 activati...

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Veröffentlicht in:Cell metabolism Jg. 26; H. 3; S. 558
Hauptverfasser: Thwe, Phyu M, Pelgrom, Leonard R, Cooper, Rachel, Beauchamp, Saritha, Reisz, Julie A, D'Alessandro, Angelo, Everts, Bart, Amiel, Eyal
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 05.09.2017
Schlagworte:
Animals
Cell Differentiation - drug effects
Cell Respiration - drug effects
Cell Survival - drug effects
Cellular Reprogramming - drug effects
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - ultrastructure
Glycogen - metabolism
Glycogen Phosphorylase - antagonists & inhibitors
Glycogen Phosphorylase - metabolism
Glycolysis - drug effects
Hypoglycemia - pathology
Lipopolysaccharides - pharmacology
Mice
Mitochondria - drug effects
Mitochondria - metabolism
dendritic cells
glycogen
glycogenolysis
glycogen shunt
glycolysis
PYG
ISSN:1932-7420, 1932-7420
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2017.08.012