Metabolic reprogramming in macrophages and dendritic cells in innate immunity
By B. Kelly, Luke A. O'Neill. Cell Research, 2015
1,714 citations recorded by the source corpus.
Activation of macrophages and dendritic cells (DCs) by pro-inflammatory stimuli causes them to undergo a metabolic switch towards glycolysis and away from oxidative phosphorylation (OXPHOS), similar to the Warburg effect in tumors. However, it is only recently that the mechanisms responsible for this metabolic reprogramming have been elucidated in more detail. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role under conditions of both hypoxia and normoxia. The withdrawal of citrate from the tricarboxylic acid (TCA) cycle has been shown to be critical for lipid biosynthesis in both macrophages and DCs. Interference with this process actually abolishes the ability of DCs to activate T cells. Another TCA cycle intermediate, succinate, activates HIF-1α and promotes inflammatory gene expression. These new insights are providing us with a deeper understanding of the role of metabolic reprogramming in innate immunity.
Subfields: Cancer Research, Immunology
View Paper: https://www.semanticscholar.org/paper/88bdfcc9b68eb02fbf6f280b8fc27ffdf6e0c945
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Citations in the corpus
- The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. (2020, background): “In proinflammatory conditions, cells generally switch between oxidative phosphorylation and glycolysis (Geltink et al., 2018; Kelly and O'Neill, 2015).”
- The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages (2019, background): “LPS treated macrophages show increased glycolysis, inhibition of AMPK, increase of mTOR signaling, as well as reduced carbohydrate kinase-like protein (CARKL) mRNA that flux into the pentose phosphate pathway (Kelly and O’Neill, 2015).”
- Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation (2016, background): “…adaptation is transcriptionally controlled (e.g., via modulation ofNos2 andCox2), succinate rep- resentsanexampleofametabolite thataffectsmajor inflammatory pathways in both immune and non-immune cells by controlling IL-1b expression, HIF-1a activity, and ROS production (Kelly and O’Neill, 2015).”
- Cellular and inter-cellular rewiring of the human colon during ulcerative colitis (2019, background): “Enterocytes also induced HIF1 pathways, a contributor to the glycolytic shift in monocytes (Kelly and O’Neill, 2015).”
- The Metabolic Signature of Macrophage Responses (2019, background): “Interestingly, macrophages express GPR91 and, in response to inflammatory signals like LPS, they activate a GPR91-mediated signal transduction that sustains the proinflammatory phenotype and leads to IL-1β production [(117, 118); Figure 3].”