Key Points
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This Review provides an introduction to dendritic cell subsets and biology, and the reasons for studying the metabolism of these cells.
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We discuss the role of different metabolic pathways in dendritic cell development and in their steady-state biology, and explain how metabolic switches underpin dendritic cell activation.
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We explain how signalling by intracellular and extracellular metabolites regulates dendritic cell biology.
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Finally, we discuss the reciprocal roles of metabolism and pathways for sensing danger in regulating dendritic cell responses.
Abstract
The past 15 years have seen enormous advances in our understanding of the receptor and signalling systems that allow dendritic cells (DCs) to respond to pathogens or other danger signals and initiate innate and adaptive immune responses. We are now beginning to appreciate that many of these pathways not only stimulate changes in the expression of genes that control DC immune functions, but also affect metabolic pathways, thereby integrating the cellular requirements of the activation process. In this Review, we focus on this relatively new area of research and attempt to describe an integrated view of DC immunometabolism.
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Acknowledgements
The authors have benefitted greatly from discussions about immune cell metabolism with E. Pearce, S. Huang, E. Amiel, R. Van der Windt, D. O'Sullivan, C.-H. Chang, C. Krawczyk, R. Jones, A. Jha, E. Driggers and M. Artymov. Their research is supported by the US National Institutes of Health (E.J.P.) and the Netherlands Organization for Scientific Research (B.E.).
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Glossary
- Electron transport chain
-
(ETC). The electron transport chain links nutrient oxidation to ATP production by oxidative phosphorylation. It consists of complexes I–V in the mitochondrial inner membrane.
- Tricarboxylic acid cycle
-
(TCA cycle; also known as the Krebs cycle or citric acid cycle). This pathway catalyses the oxidation of acetyl-CoA (from glucose or fatty acids, or indirectly from amino acids) to generate NADH and FADH, which fuel the electron transport chain and thereby oxidative phosphorylation and ATP production. It also serves as a source of precursors for amino acid and lipid synthesis.
- Bone marrow-derived DCs
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(BMDCs). These monocyte-derived dendritic cells (DCs) are generated from bone marrow cultures supplemented with granulocyte–macrophage colony-stimulating factor and are used to model the behaviour of DCs that develop from monocytes under inflammatory conditions in vivo.
- Spare respiratory capacity
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The amount of energy generating capacity, beyond that needed for basal biology, that a cell maintains in reserve to be used when called upon.
- M1 macrophages
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Macrophages that have been activated by a Toll-like receptor agonist, usually in combination with interferon-γ.
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Pearce, E., Everts, B. Dendritic cell metabolism. Nat Rev Immunol 15, 18–29 (2015). https://doi.org/10.1038/nri3771
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DOI: https://doi.org/10.1038/nri3771
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