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Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels
Nature Communications, Volume: 8, Issue: 1
Swansea University Author: Luke Davies
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DOI (Published version): 10.1038/s41467-017-02092-0
The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage...
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The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage functions. We find the peritoneum to be rich in glutamate, a glutaminolysis-fuel that is exploited by peritoneal-resident macrophages to maintain respiratory burst during phagocytosis via enhancing mitochondrial complex-II metabolism. This niche-supported, inducible mitochondrial function is dependent on protein kinase C activity, and is required to fine-tune the cytokine responses that control inflammation. In addition, we find that peritoneal-resident macrophage mitochondria are recruited to phagosomes and produce mitochondrially derived reactive oxygen species, which are necessary for microbial killing. We propose that tissue-resident macrophages are metabolically poised in situ to protect and exploit their tissue-niche by utilising locally available fuels to implement specific metabolic programmes upon microbial sensing.
Faculty of Medicine, Health and Life Sciences
This work has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, Intramural Research Program, USA and the Henry Wellcome Trust, UK (WT103973MA). P.R.T. is funded by the Wellcome Trust (107964/Z/15/Z). D.B.K. is under Contract No. HHSN261200800001E.