title: Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation.
abstract: Dendritic cells (DCs) are key regulators of innate and acquired immunity. The maturation of DCs is directed by signal transduction events downstream of toll-like receptors (TLRs) and other pattern recognition receptors. Here, we demonstrate that, in mouse DCs, TLR agonists stimulate a profound metabolic transition to aerobic glycolysis, similar to the Warburg metabolism displayed by cancer cells. This metabolic switch depends on the phosphatidyl inositol 3'-kinase/Akt pathway, is antagonized by the adenosine monophosphate (AMP)-activated protein kinase (AMPK), and is required for DC maturation. The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10. Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Krawczyk
authors.forename: Thomas
authors.initials: T
authors.lastname: Holowka
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Julianna
authors.initials: J
authors.lastname: Blagih
authors.forename: Eyal
authors.initials: E
authors.lastname: Amiel
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.forename: Justin R
authors.initials: JR
authors.lastname: Cross
authors.forename: Euihye
authors.initials: E
authors.lastname: Jung
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt