PMID- 20351312
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20220311
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 23
DP  - 2010 Jun 10
TI  - Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic 
      cell activation.
PG  - 4742-9
LID - 10.1182/blood-2009-10-249540 [doi]
AB  - 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.
FAU - Krawczyk, Connie M
AU  - Krawczyk CM
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, USA.
FAU - Holowka, Thomas
AU  - Holowka T
FAU - Sun, Jie
AU  - Sun J
FAU - Blagih, Julianna
AU  - Blagih J
FAU - Amiel, Eyal
AU  - Amiel E
FAU - DeBerardinis, Ralph J
AU  - DeBerardinis RJ
FAU - Cross, Justin R
AU  - Cross JR
FAU - Jung, Euihye
AU  - Jung E
FAU - Thompson, Craig B
AU  - Thompson CB
FAU - Jones, Russell G
AU  - Jones RG
FAU - Pearce, Edward J
AU  - Pearce EJ
LA  - eng
GR  - MOP-93 799/CAPMC/CIHR/Canada
GR  - R01 AI053825/AI/NIAID NIH HHS/United States
GR  - AI53825/AI/NIAID NIH HHS/United States
GR  - CA104838/CA/NCI NIH HHS/United States
GR  - T32 AI049823/AI/NIAID NIH HHS/United States
GR  - P01 CA104838/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100329
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Toll-Like Receptors)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/*immunology/metabolism
MH  - Glycolysis/genetics/*immunology
MH  - Inflammation/genetics/immunology/metabolism
MH  - Interleukin-10/genetics/immunology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Phosphatidylinositol 3-Kinases/genetics/immunology/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/immunology/metabolism
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptors/antagonists & inhibitors/genetics/*immunology/metabolism
PMC - PMC2890190
EDAT- 2010/03/31 06:00
MHDA- 2010/07/20 06:00
PMCR- 2011/06/10
CRDT- 2010/03/31 06:00
PHST- 2010/03/31 06:00 [entrez]
PHST- 2010/03/31 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
PHST- 2011/06/10 00:00 [pmc-release]
AID - S0006-4971(20)34893-X [pii]
AID - 2009/249540 [pii]
AID - 10.1182/blood-2009-10-249540 [doi]
PST - ppublish
SO  - Blood. 2010 Jun 10;115(23):4742-9. doi: 10.1182/blood-2009-10-249540. Epub 2010 
      Mar 29.