4.8 Article

Fish Macrophages Show Distinct Metabolic Signatures Upon Polarization

Journal

FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.00152

Keywords

M1 M2 macrophage polarization; metabolic reprogramming; teleost; glycolysis; oxidative phosphorylation (OXPHOS); oxidative metabolism; Seahorse; extracellular flux analysis

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Funding

  1. European Commission under the 8th (H2020) Framework Program for Research and Technological Development of the European Union (PARAFISHCONTROL Grant) [634429]
  2. NWO-WIAS Graduate Programme 2016 Grant [Wageningen Institute of Animal Sciences (WIAS)]
  3. NWO-WIAS Graduate Programme 2016 Grant [Dutch Organization for Scientific Research (NWO)]

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Macrophages play important roles in conditions ranging from host immune defense to tissue regeneration and polarize their functional phenotype accordingly. Next to differences in the use of L-arginine and the production of different cytokines, inflammatory M1 macrophages and anti-inflammatory M2 macrophages are also metabolically distinct. In mammals, M1 macrophages show metabolic reprogramming toward glycolysis, while M2 macrophages rely on oxidative phosphorylation to generate energy. The presence of polarized functional immune phenotypes conserved from mammals to fish led us to hypothesize that a similar metabolic reprogramming in polarized macrophages exists in carp. We studied mitochondrial function of M1 and M2 carp macrophages under basal and stressed conditions to determine oxidative capacity by real-time measurements of oxygen consumption and glycolytic capacity by measuring lactate-based acidification. In M1 macrophages, we found increased nitric oxide production and irg1 expression in addition to altered oxidative phosphorylation and glycolysis. In M2 macrophages, we found increased arginase activity, and both oxidative phosphorylation and glycolysis were similar to control macrophages. These results indicate that M1 and M2 carp macrophages show distinct metabolic signatures and indicate that metabolic reprogramming may occur in carp M1 macrophages. This immunometabolic reprogramming likely supports the inflammatory phenotype of polarized macrophages in teleost fish such as carp, similar to what has been shown in mammals.

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