PMID- 32183271 OWN - NLM STAT- MEDLINE DCOM- 20210311 LR - 20210311 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 3 DP - 2020 Mar 14 TI - Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists. LID - 10.3390/cells9030715 [doi] LID - 715 AB - 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 beta-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. FAU - Curtis, Kylie D AU - Curtis KD AD - Undergraduate student researcher or research employee, University of Vermont, Burlington, VT 05405, USA. FAU - Smith, Portia R AU - Smith PR AD - Undergraduate student researcher or research employee, University of Vermont, Burlington, VT 05405, USA. FAU - Despres, Hannah W AU - Despres HW AUID- ORCID: 0000-0003-0321-5202 AD - Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA. FAU - Snyder, Julia P AU - Snyder JP AD - Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA. FAU - Hogan, Tyler C AU - Hogan TC AD - Undergraduate student researcher or research employee, University of Vermont, Burlington, VT 05405, USA. FAU - Rodriguez, Princess D AU - Rodriguez PD AD - Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA. FAU - Amiel, Eyal AU - Amiel E AUID- ORCID: 0000-0002-1578-8705 AD - Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT 05405, USA. LA - eng GR - P30 GM118228/GM/NIGMS NIH HHS/United States GR - T32 AI055402/AI/NIAID NIH HHS/United States GR - R21 AI135385/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200314 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Lectins, C-Type) RN - 0 (Toll-Like Receptors) RN - 9005-79-2 (Glycogen) SB - IM MH - Dendritic Cells/*metabolism MH - Glycogen/*metabolism MH - Glycolysis/*immunology MH - Humans MH - Immunity, Innate/*immunology MH - Lectins, C-Type/*metabolism MH - Toll-Like Receptors/*metabolism PMC - PMC7140704 OTO - NOTNLM OT - dendritic cells OT - glucose OT - glycogen OT - glycolysis OT - innate immunity OT - metabolism COIS- The authors declare no conflict of interest. EDAT- 2020/03/19 06:00 MHDA- 2021/03/12 06:00 PMCR- 2020/03/01 CRDT- 2020/03/19 06:00 PHST- 2020/01/28 00:00 [received] PHST- 2020/03/09 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/03/19 06:00 [entrez] PHST- 2020/03/19 06:00 [pubmed] PHST- 2021/03/12 06:00 [medline] PHST- 2020/03/01 00:00 [pmc-release] AID - cells9030715 [pii] AID - cells-09-00715 [pii] AID - 10.3390/cells9030715 [doi] PST - epublish SO - Cells. 2020 Mar 14;9(3):715. doi: 10.3390/cells9030715.