Cargando…

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

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 (...

Descripción completa

Detalles Bibliográficos
Autores principales: Curtis, Kylie D., Smith, Portia R., Despres, Hannah W., Snyder, Julia P., Hogan, Tyler C., Rodriguez, Princess D., Amiel, Eyal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140704/
https://www.ncbi.nlm.nih.gov/pubmed/32183271
http://dx.doi.org/10.3390/cells9030715
_version_ 1783519051805360128
author Curtis, Kylie D.
Smith, Portia R.
Despres, Hannah W.
Snyder, Julia P.
Hogan, Tyler C.
Rodriguez, Princess D.
Amiel, Eyal
author_facet Curtis, Kylie D.
Smith, Portia R.
Despres, Hannah W.
Snyder, Julia P.
Hogan, Tyler C.
Rodriguez, Princess D.
Amiel, Eyal
author_sort Curtis, Kylie D.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7140704
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71407042020-04-13 Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists Curtis, Kylie D. Smith, Portia R. Despres, Hannah W. Snyder, Julia P. Hogan, Tyler C. Rodriguez, Princess D. Amiel, Eyal Cells Article 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. MDPI 2020-03-14 /pmc/articles/PMC7140704/ /pubmed/32183271 http://dx.doi.org/10.3390/cells9030715 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Curtis, Kylie D.
Smith, Portia R.
Despres, Hannah W.
Snyder, Julia P.
Hogan, Tyler C.
Rodriguez, Princess D.
Amiel, Eyal
Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title_full Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title_fullStr Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title_full_unstemmed Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title_short Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
title_sort glycogen metabolism supports early glycolytic reprogramming and activation in dendritic cells in response to both tlr and syk-dependent clr agonists
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140704/
https://www.ncbi.nlm.nih.gov/pubmed/32183271
http://dx.doi.org/10.3390/cells9030715
work_keys_str_mv AT curtiskylied glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT smithportiar glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT despreshannahw glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT snyderjuliap glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT hogantylerc glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT rodriguezprincessd glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists
AT amieleyal glycogenmetabolismsupportsearlyglycolyticreprogrammingandactivationindendriticcellsinresponsetobothtlrandsykdependentclragonists