Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation

Connie M. Krawczyk, Thomas Holowka, Jie Sun, Julianna Blagih, Eyal Amiel, Ralph J. DeBerardinis, Justin R. Cross, Euihye Jung, Craig B. Thompson, Russell G. Jones, Edward J. Pearce

Research output: Contribution to journalArticle

518 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4742-4749
Number of pages8
JournalBlood
Volume115
Issue number23
DOIs
StatePublished - Jun 10 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., & Pearce, E. J. (2010). Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood, 115(23), 4742-4749. https://doi.org/10.1182/blood-2009-10-249540