Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages.

Macrophages are innate immune cells that adopt diverse activation states in response to their microenvironment. Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is of high interest. Here, we find that mouse and human M1 macrophages fail to convert into M2 cells upon IL-4 exposure in vitro and in vivo. In sharp contrast, M2 macrophages are more plastic and readily repolarized into an inflammatory M1 state. We identify M1-associated inhibition of mitochondrial oxidative phosphorylation as the factor responsible for preventing M1→M2 repolarization. Inhibiting nitric oxide production, a key effector molecule in M1 cells, dampens the decline in mitochondrial function to improve metabolic and phenotypic reprogramming to M2 macrophages. Thus, inflammatory macrophage activation blunts oxidative phosphorylation, thereby preventing repolarization. Therapeutically restoring mitochondrial function might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control disease.

Van den Bossche J ，Baardman J ，Otto NA ，van der Velden S ，Neele AE ，van den Berg SM ，Luque-Martin R ，Chen HJ ，Boshuizen MC ，Ahmed M ，Hoeksema MA ，de Vos AF ，de Winther MP ... -  《Cell Reports》

Fish Macrophages Show Distinct Metabolic Signatures Upon Polarization.

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.

Wentzel AS ，Janssen JJE ，de Boer VCJ ，van Veen WG ，Forlenza M ，Wiegertjes GF ... -  《Frontiers in Immunology》

Alternative reprogramming of M1/M2 phenotype of mouse peritoneal macrophages in vitro with interferon-γ and interleukin-4.

Lyamina SV ，Kruglov SV ，Vedenikin TY ，Borodovitsyna OA ，Suvorova IA ，Shimshelashvili ShL ，Malyshev IY ... -  《-》

Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic shift.

Scrima R ，Menga M ，Pacelli C ，Agriesti F ，Cela O ，Piccoli C ，Cotoia A ，De Gregorio A ，Gefter JV ，Cinnella G ，Capitanio N ... -  《PLoS One》

Pyropia yezoensis glycoprotein promotes the M1 to M2 macrophage phenotypic switch via the STAT3 and STAT6 transcription factors.

Choi JW ，Kwon MJ ，Kim IH ，Kim YM ，Lee MK ，Nam TJ ... -  《-》