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

作者：Krawczyk Connie M; Holowka Thomas; Sun Jie; Blagih Julianna; Amiel Eyal; DeBerardinis Ralph J; Cross Justin R; Jung Euihye; Thompson Craig B; Jones Russell G; Pearce Edward J^*

来源：Blood, 2010, 115(23): 4742-4749.

DOI：10.1182/blood-2009-10-249540

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. (Blood. 2010;115(23):4742-4749)

• 出版日期2010-6-10