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INFLAMMATION

DAMP-driven metabolic adaptation

Nature Reviews Immunology volume 20, page 1 (2020)Cite this article

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Pathogen-associated molecular patterns such as lipopolysaccharide (LPS) both induce the expression of inflammatory cytokines such as IL-1β and lead to changes in macrophage metabolism that involve a shift from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis. While it is known that endogenous damage-associated molecular patterns (DAMPs), such as oxidized phospholipids, can similarly induce inflammatory gene expression and inflammasome activation, it has not been known whether they also drive metabolic adaptation. A new study in Nature Immunology shows that a class of oxidized phospholipids known as oxPAPC can indeed induce a unique ‘hypermetabolic’ state in macrophages.

In keeping with the known influence of macrophage metabolism on inflammatory cytokine production, the production of pro-IL-1β was markedly increased in cells exposed to LPS and oxPAPC (co-treated cells) compared with LPS only. Further studies showed that inhibiting OXPHOS decreased the capacity of the hypermetabolic macrophages to produce IL-1β. OXPHOS is normally inhibited in cells exposed to LPS through the production of nitric oxide, but the authors showed that oxPAPC administration to LPS-treated macrophages inhibits nitric oxide production in a dose-dependent manner by decreasing levels of inducible nitric oxide synthase. In addition to OXPHOS, glutaminolysis was also required for the increased production of IL-1β by co-treated macrophages, and oxPAPC was shown to increase the transcription of several genes involved in glutamine transport and metabolism. Thus, oxPAPC promotes OXPHOS and stimulates glutamine metabolism, which together contribute to a hyperinflammatory state.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Kirsty Minton

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  1. Kirsty Minton
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Correspondence to Kirsty Minton.

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Minton, K. DAMP-driven metabolic adaptation. Nat Rev Immunol 20, 1 (2020). https://doi.org/10.1038/s41577-019-0258-9

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