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Nat Commun. 2017 Dec 12;8(1):2074. doi: 10.1038/s41467-017-02092-0.

Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels.

Author information

1
Division of Infection & Immunity, School of Medicine, Cardiff University, Tenovus Building, Heath Park, CF14 4XN, UK. davieslc6@cf.ac.uk.
2
Cancer & Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA. davieslc6@cf.ac.uk.
3
Cancer & Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA.
4
Division of Infection & Immunity, School of Medicine, Cardiff University, Tenovus Building, Heath Park, CF14 4XN, UK.
5
Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
6
Cancer & Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA. mcvicard@mail.nih.gov.

Abstract

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.

PMID:
29234000
PMCID:
PMC5727035
DOI:
10.1038/s41467-017-02092-0
[Indexed for MEDLINE]
Free PMC Article

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