2010
DOI: 10.1182/blood-2009-10-249540
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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 m… Show more

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Cited by 971 publications
(1,148 citation statements)
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“…Warburg went on to conclude, however, in 1958 that this "cancer metabolism" did not occur in leukocytes, his opinion being that the observation of aerobic glycolysis in these cells was an artifact of preparation (10). This proved to be an incorrect conclusion because we now know that a switch in metabolism from oxidative phosphorylation to glycolysis occurs following activation of macrophages and dendritic cells (DCs) by LPS (6,11), in a similar manner to the Warburg effect observed in tumor cells (9). A metabolomic screen and microarray analysis in macrophages activated by LPS have confirmed this switch from oxidative phosphorylation to glycolysis.…”
Section: The Warburg Effect In Activated Macrophagesmentioning
confidence: 97%
See 1 more Smart Citation
“…Warburg went on to conclude, however, in 1958 that this "cancer metabolism" did not occur in leukocytes, his opinion being that the observation of aerobic glycolysis in these cells was an artifact of preparation (10). This proved to be an incorrect conclusion because we now know that a switch in metabolism from oxidative phosphorylation to glycolysis occurs following activation of macrophages and dendritic cells (DCs) by LPS (6,11), in a similar manner to the Warburg effect observed in tumor cells (9). A metabolomic screen and microarray analysis in macrophages activated by LPS have confirmed this switch from oxidative phosphorylation to glycolysis.…”
Section: The Warburg Effect In Activated Macrophagesmentioning
confidence: 97%
“…LPS has been shown to decrease AMPK activation, whereas activation of AMPK results in a decrease in NF-B activation and TNF␣ production in macrophages following stimulation with inflammatory stimuli such as LPS (45). Knockdown of AMPK enhances LPS-induced IL-12p40 expression in DCs (11). AMPK-␣1 Ϫ/Ϫ mice are more prone to severe experimental autoimmune encephalomyelitis in comparison with controls, whereas spleen cells isolated from these mice secrete more IFN␥ and less IL-17 following antigen stimulation.…”
Section: Role Of Nad ؉ Sirtuins and Amp-dependent Protein Kinase Imentioning
confidence: 99%
“…It is now clear that acute and chronic inflammatory responses can add to the total tissue injury that occurs, making it important to identify how it is regulated. Complex interactions are occurring between inflammation and metabolism, and their importance is increasingly appreciated with the identification of mechanistic pathways (10,27,29). One aspect of this interrelationship is the change in metabolism that occurs with the initiation of inflammation.…”
Section: Discussionmentioning
confidence: 99%
“…In recent years it has become evident that immune cells have the ability to shift their metabolism under varying conditions and that this is essential for proper immune function [2]. Stimulation of DCs and macrophages can result in a decrease in oxidative phosphorylation, which is normally employed under resting conditions, with a concomitant increase in glycolysis and the pentose-phosphate pathway [3,4]. This switch to glycolysis rapidly generates ATP to maintain mitochondrial membrane potential and energy homeostasis, ultimately ensuring cell viability [5].…”
mentioning
confidence: 99%