PMID- 31509298 OWN - NLM STAT- MEDLINE DCOM- 20200603 LR - 20211204 IS - 1938-3673 (Electronic) IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 106 IP - 6 DP - 2019 Dec TI - Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1beta production to beta-glucan ligands in a TLR-independent manner. PG - 1325-1335 LID - 10.1002/JLB.3A0819-207RR [doi] AB - Dendritic cells (DCs) activated via TLR ligation experience metabolic reprogramming, in which the cells are heavily dependent on glucose and glycolysis for the synthesis of molecular building blocks essential for maturation, cytokine production, and the ability to stimulate T cells. Although the TLR-driven metabolic reprogramming events are well documented, fungal-mediated metabolic regulation via C-type lectin receptors such as Dectin-1 and Dectin-2 is not clearly understood. Here, we show that activation of DCs with fungal-associated beta-glucan ligands induces acute glycolytic reprogramming that supports the production of IL-1beta and its secretion subsequent to NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. This acute glycolytic induction in response to beta-glucan ligands requires spleen tyrosine kinase signaling in a TLR-independent manner, suggesting now that different classes of innate immune receptors functionally induce conserved metabolic responses to support immune cell activation. These studies provide new insight into the complexities of metabolic regulation of DCs immune effector function regarding cellular activation associated with protection against fungal microbes. CI - (c)2019 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc. FAU - Thwe, Phyu M AU - Thwe PM AD - Cellular, Molecular, and Biomedical (CMB) Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA. FAU - Fritz, Daniel I AU - Fritz DI AD - University of Vermont, Burlington, Vermont, USA. FAU - Snyder, Julia P AU - Snyder JP AD - Cellular, Molecular, and Biomedical (CMB) Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA. FAU - Smith, Portia R AU - Smith PR AD - University of Vermont, Burlington, Vermont, USA. FAU - Curtis, Kylie D AU - Curtis KD AD - University of Vermont, Burlington, Vermont, USA. FAU - O'Donnell, Alexandra AU - O'Donnell A AD - University of Vermont, Burlington, Vermont, USA. FAU - Galasso, Nicholas A AU - Galasso NA AD - University of Vermont, Burlington, Vermont, USA. FAU - Sepaniac, Leslie A AU - Sepaniac LA AD - Cellular, Molecular, and Biomedical (CMB) Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA. FAU - Adamik, Benjamin J AU - Adamik BJ AD - University of Vermont, Burlington, Vermont, USA. FAU - Hoyt, Laura R AU - Hoyt LR AD - University of Vermont, Burlington, Vermont, USA. FAU - Rodriguez, Princess D AU - Rodriguez PD AD - Cellular, Molecular, and Biomedical (CMB) Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA. FAU - Hogan, Tyler C AU - Hogan TC AD - University of Vermont, Burlington, Vermont, USA. FAU - Schmidt, Andrea F AU - Schmidt AF AD - University of Vermont, Burlington, Vermont, USA. FAU - Poynter, Matthew E AU - Poynter ME AD - Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, Vermont, USA. FAU - Amiel, Eyal AU - Amiel E AUID- ORCID: 0000-0002-1578-8705 AD - Department of Biomedical and Health Sciences, University of Vermont, Burlington, Vermont, USA. LA - eng GR - R01 HL142081/HL/NHLBI NIH HHS/United States GR - T32 AI055402/AI/NIAID NIH HHS/United States GR - P30 GM118228/GM/NIGMS NIH HHS/United States GR - R21 AI135385/AI/NIAID NIH HHS/United States GR - R01 HL133920/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190911 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Interleukin-1beta) RN - 0 (Lectins, C-Type) RN - 0 (Ligands) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Toll-Like Receptors) RN - 0 (beta-Glucans) RN - EC 2.7.1.- (Tbk1 protein, mouse) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (Syk protein, mouse) RN - EC 2.7.11.1 (Akt1 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Dendritic Cells/immunology/*metabolism MH - Glycolysis MH - Interleukin-1beta/*biosynthesis MH - Lectins, C-Type/metabolism MH - Ligands MH - Mice MH - Myeloid Differentiation Factor 88/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction MH - Syk Kinase/genetics/*metabolism MH - Toll-Like Receptors/*metabolism MH - beta-Glucans/*metabolism PMC - PMC6883127 MID - NIHMS1047959 OTO - NOTNLM OT - NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) OT - dectin-1/2 OT - dendritic cells (DCs) OT - glycolysis OT - inflammasome OT - oxidative phosphorylation (OXPHOS) OT - pattern recognition receptor (PRR) OT - spleen tyrosine kinase (Syk) OT - toll-like receptor (TLR) COIS- The authors declare no conflicts of interest. EDAT- 2019/09/12 06:00 MHDA- 2020/06/04 06:00 PMCR- 2019/12/08 CRDT- 2019/09/12 06:00 PHST- 2018/05/31 00:00 [received] PHST- 2019/08/23 00:00 [revised] PHST- 2019/08/23 00:00 [accepted] PHST- 2019/09/12 06:00 [pubmed] PHST- 2020/06/04 06:00 [medline] PHST- 2019/09/12 06:00 [entrez] PHST- 2019/12/08 00:00 [pmc-release] AID - JLB10486 [pii] AID - 10.1002/JLB.3A0819-207RR [doi] PST - ppublish SO - J Leukoc Biol. 2019 Dec;106(6):1325-1335. doi: 10.1002/JLB.3A0819-207RR. Epub 2019 Sep 11.