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. 2017 Mar 15;8:289. doi: 10.3389/fimmu.2017.00289

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Copyright © 2017 Geeraerts, Bolli, Fendt and Van Ginderachter.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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M1 macrophage metabolism. M1 macrophage metabolism is characterized by enhanced aerobic glycolysis, converting glucose into lactate. M1 macrophages have an increased flux through the pentose phosphate pathway (PPP), generating NADPH, used for the generation of the anti-oxidant glutathione (GSH) and the inflammatory mediators nitric oxide (NO) and reactive oxygen species (ROS). In M1 macrophages, the tricarboxylic acid (TCA) cycle is broken in two places, leading to the accumulation of succinate and citrate. While the accumulation of succinate leads to HIF-1α stabilization and the transcription of pro-inflammatory and glycolytic genes, citrate is used for the generation of fatty acids, NO, ROS, and the synthesis of itaconate. Another aspect of M1 macrophage metabolism is the conversion of l-arginine to NO and l-citrulline. All important metabolic reactions present in M1/M2 macrophages are shown in black, reactions shown in gray are absent or less pronounced. The metabolic pathways strongly upregulated by M1/M2 macrophage polarization are highlighted by a colored shadow, the width of the shadow illustrates the weight of a particular pathway in the macrophage activation state. All metabolic enzymes are indicated in green. Dotted lines represent impaired metabolic reactions. Abbreviations: α-KG: α-ketoglutarate; AASS: aspartate–arginosuccinate shunt pathway; ACLY: ATP-citrate lyase; CAD: cis-aconitate decarboxylase; CIC: mitochondrial citrate carrier; ETC: electron transport chain; FAS: fatty acid synthase; GLUT: glucose transporter; HK: hexokinase; IDH: isocitrate dehydrogenase; iNOS: inducible nitric oxide synthase; LDH: lactate dehydrogenase; MCT: monocarboxylate transporter; ME: malic enzyme; OAA: oxaloacetate; PEP: phosphoenolpyruvate; PDH: pyruvate dehydrogenase; PFK: phosphofructokinase; SDH: succinate dehydrogenase; SLC: solute carrier.