TY - JOUR
T1 - Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1β production to β-glucan ligands in a TLR-independent manner
AU - Thwe, Phyu M.
AU - Fritz, Daniel I.
AU - Snyder, Julia P.
AU - Smith, Portia R.
AU - Curtis, Kylie D.
AU - O'Donnell, Alexandra
AU - Galasso, Nicholas A.
AU - Sepaniac, Leslie A.
AU - Adamik, Benjamin J.
AU - Hoyt, Laura R.
AU - Rodriguez, Princess D.
AU - Hogan, Tyler C.
AU - Schmidt, Andrea F.
AU - Poynter, Matthew E.
AU - Amiel, Eyal
N1 - Funding Information:
We specially acknowledge Dr. Paula Deming (and the Department of Biomedical and Health Sciences at UVM) and Dr. Ralph Budd (and the UVM VCIID COBRE) for extensive support. We additionally acknowledge and thank Roxana del Rio-Guerra, Flow Cytometry and Cell Sorting Facility Manager of the UVM-COM Flow Cytometry and Cell Sorting Facility. Funding sources: AAI Careers in Immunology Fellowship (P.M.T., E.A.), UVM start-up Funds (E.A.), UVM CNHS Incentive Grant (E.A.), P30GM118228 (E.A.), and NIH NIAID 1R21AI135385-01A1 grant (E.A.).
Funding Information:
We specially acknowledge Dr. Paula Deming (and the Department of Biomedical and Health Sciences at UVM) and Dr. Ralph Budd (and the UVM VCIID COBRE) for extensive support. We additionally acknowledge and thank Roxana del Rio‐Guerra, Flow Cytometry and Cell Sorting Facility Manager of the UVM‐COM Flow Cytometry and Cell Sorting Facility. Funding sources: AAI Careers in Immunology Fellowship (P.M.T., E.A.), UVM start‐up Funds (E.A.), UVM CNHS Incentive Grant (E.A.), P30GM118228 (E.A.), and NIH NIAID 1R21AI135385‐01A1 grant (E.A.).
Publisher Copyright:
© 2019 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 β-glucan ligands induces acute glycolytic reprogramming that supports the production of IL-1β and its secretion subsequent to NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. This acute glycolytic induction in response to β-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.
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 β-glucan ligands induces acute glycolytic reprogramming that supports the production of IL-1β and its secretion subsequent to NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. This acute glycolytic induction in response to β-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.
KW - NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3)
KW - dectin-1/2
KW - dendritic cells (DCs)
KW - glycolysis
KW - inflammasome
KW - oxidative phosphorylation (OXPHOS)
KW - pattern recognition receptor (PRR)
KW - spleen tyrosine kinase (Syk)
KW - toll-like receptor (TLR)
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UR - http://www.scopus.com/inward/citedby.url?scp=85072225341&partnerID=8YFLogxK
U2 - 10.1002/JLB.3A0819-207RR
DO - 10.1002/JLB.3A0819-207RR
M3 - Article
C2 - 31509298
AN - SCOPUS:85072225341
VL - 106
SP - 1325
EP - 1335
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -