scholarly journals Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 715 ◽  
Author(s):  
Kylie D. Curtis ◽  
Portia R. Smith ◽  
Hannah W. Despres ◽  
Julia P. Snyder ◽  
Tyler C. Hogan ◽  
...  

Dendritic cells (DCs) increase their metabolic dependence on glucose and glycolysis to support their maturation, activation-associated cytokine production, and T-cell stimulatory capacity. We have previously shown that this increase in glucose metabolism can be initiated by both Toll-like receptor (TLR) and C-type lectin receptor (CLR) agonists. In addition, we have shown that the TLR-dependent demand for glucose is partially satisfied by intracellular glycogen stores. However, the role of glycogen metabolism in supporting CLR-dependent DC glycolytic demand has not been formally demonstrated. In this work, we have shown that DCs activated with fungal-associated β-glucan ligands exhibit acute glycolysis induction that is dependent on glycogen metabolism. Furthermore, glycogen metabolism supports DC maturation, inflammatory cytokine production, and priming of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in response to both TLR- and CLR-mediated activation. These data support a model in which different classes of innate immune receptors functionally converge in their requirement for glycogen-dependent glycolysis to metabolically support early DC activation. These studies provide new insight into how DC immune effector function is metabolically regulated in response to diverse inflammatory stimuli.

2011 ◽  
Vol 12 (1) ◽  
pp. 57 ◽  
Author(s):  
Anna Sanecka ◽  
Marleen Ansems ◽  
Amy C Prosser ◽  
Katharina Danielski ◽  
Kathrin Warner ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1808 ◽  
Author(s):  
Allison K. Meyers ◽  
Xuewei Zhu

In response to inflammatory stimuli, immune cells reconfigure their metabolism and bioenergetics to generate energy and substrates for cell survival and to launch immune effector functions. As a critical component of the innate immune system, the nucleotide-binding and oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome can be activated by various endogenous and exogenous danger signals. Activation of this cytosolic multiprotein complex triggers the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and initiates pyroptosis, an inflammatory form of programmed cell death. The NLRP3 inflammasome fuels both chronic and acute inflammatory conditions and is critical in the emergence of inflammaging. Recent advances have highlighted that various metabolic pathways converge as potent regulators of the NLRP3 inflammasome. This review focuses on our current understanding of the metabolic regulation of the NLRP3 inflammasome activation, and the contribution of the NLRP3 inflammasome to inflammaging.


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