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

Luke C Davies, Christopher M Rice, Erika M Palmieri, Philip R Taylor, Douglas B Kuhns, Daniel W McVicar

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.

Original languageEnglish
Pages (from-to)2074
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 12 Dec 2017

Keywords

  • Animals
  • Electron Transport Complex II/metabolism
  • Female
  • Glutamic Acid/metabolism
  • Inflammation/immunology
  • Macrophages, Peritoneal/cytology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria/metabolism
  • Peritoneum/cytology
  • Phagocytosis/immunology
  • Phagosomes/immunology
  • Primary Cell Culture
  • Protein Kinase C/metabolism
  • Reactive Oxygen Species/metabolism
  • Respiratory Burst/immunology
  • Stem Cell Niche/immunology

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