Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists.
Cells
; 9(3)2020 03 14.
Article
em En
| MEDLINE
| ID: mdl-32183271
ABSTRACT
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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Lectinas Tipo C
/
Receptores Toll-Like
/
Glicogênio
/
Glicólise
/
Imunidade Inata
Limite:
Humans
Idioma:
En
Revista:
Cells
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos