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. Author manuscript; available in PMC: 2017 Sep 1.
Published in final edited form as: Nat Rev Immunol. 2016 Jul 11;16(9):553–565. doi: 10.1038/nri.2016.70

Figure 4. The TCA cycle in macrophages.

Figure 4

In M2-like macrophages (that is, interleukin-4 (IL-4)-activated macrophages) the tricarboxylic acid (TCA) cycle is intact and participates in oxidative phosphorylation, providing ATP for energy. In M1-like macrophages (that is, cells that have been activated by lipopolysaccharide (LPS) and interferon-γ), the TCA cycle is broken in two places — after citrate and after succinate. Citrate is used to generate fatty acids for membrane biogenesis and also for prostaglandin production. It also generates itaconic acid via the enzyme immune-responsive gene 1 (IRG1). Itaconic acid has direct antimicrobial activity against Mycobacterium tuberculosis and Salmonella sp. HIF1α, hypoxia-inducible factor 1α.