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. 2022 Dec 27;12:1060810. doi: 10.3389/fcimb.2022.1060810

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Copyright © 2022 Wong Fok Lung, Chan, Prince, Yeaman, Archer, Aman and Proctor

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) and the copyright owner(s) 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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Metabolic reprogramming of macrophage. During infection with live bacteria or upon stimulation with PAMPs such as LPS, macrophages become activated for pathogen clearance (pro-inflammatory M1 phenotype) by undergoing metabolic changes. These include increased glycolysis and accumulation of TCA cycle metabolites such as citrate, succinate and itaconate. Succinate stabilizes the transcription factor HIF-1α, which promotes the production of proinflammatory cytokines. Itaconate dampens the succinate-induced inflammation via its anti-inflammatory properties.