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Human and murine macrophages exhibit differential metabolic responses to lipopolysaccharide - A divergent role for glycolysis

Abstract : Macrophages adopt different phenotypes in response to microenvironmental changes, which can be principally classified into inflammatory and anti-inflammatory states. Inflammatory activation of macrophages has been linked with metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis. In contrast to mouse macrophages, little information is available on the link between metabolism and inflammation in human macrophages. In the current report it is demonstrated that lipopolysaccharide (LPS)-activated human peripheral blood monocyte-derived macrophages (hMDMs) fail to undergo metabolic reprogramming towards glycolysis, but rely on oxidative phosphorylation for the generation of ATP. By contrast, activation by LPS led to an increased extracellular acidification rate (glycolysis) and decreased oxygen consumption rate (oxidative phosphorylation) in mouse bone marrow-derived macrophages (mBMDMs). Mitochondrial bioenergetics after LPS stimulation in human macrophages was unchanged, but was markedly impaired in mouse macrophages. Furthermore, treatment with 2-deoxyglucose, an inhibitor of glycolysis, led to cell death in mouse, but not in human macrophages. Finally, glycolysis appeared to be critical for LPS-mediated induction of the anti-inflammatory cytokine interleukin-10 in both human and mouse macrophages. In summary, these findings indicate that LPS-induced immunometabolism in human macrophages is different to that observed in mouse macrophages.
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https://www.hal.inserm.fr/inserm-03215576
Contributor : Roberto Motterlini <>
Submitted on : Monday, May 3, 2021 - 2:15:39 PM
Last modification on : Friday, July 9, 2021 - 12:10:03 PM

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Vijith Vijayan, Pooja Pradhan, Laura Braud, Heiko Fuchs, Faikah Gueler, et al.. Human and murine macrophages exhibit differential metabolic responses to lipopolysaccharide - A divergent role for glycolysis. Redox Biology, Elsevier, 2019, 22, pp.101147. ⟨10.1016/j.redox.2019.101147⟩. ⟨inserm-03215576⟩

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