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Immunometabolic adaptation in monocytes underpins functional changes during pregnancy [metabolism]

ABSTRACT: Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met might also underpin changes in innate and adaptive immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Here, we use peripheral blood monocytes, susceptible to microenvironmentally determined reprogramming of metabolism, to determine if pregnancy at term provokes an altered metabolic profile that underpins functional change. Focusing on late gestation where any effect will be most profound, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism then show that reduced monocyte oxidative metabolism with pregnancy compromises the production of TNF and IL-6 in response to MDP but not LPS. Overall, mitochondrially centred metabolic capabilities of late gestation monocytes are downregulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield new therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255271 | GEO | 2024/04/01

REPOSITORIES: GEO

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Immunometabolic adaptation in monocytes underpins functional changes during pregnancy

Project description:Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met might also underpin changes in innate and adaptive immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Here, we use peripheral blood monocytes, susceptible to microenvironmentally determined reprogramming of metabolism, to determine if pregnancy at term provokes an altered metabolic profile that underpins functional change. Focusing on late gestation where any effect will be most profound, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism then show that reduced monocyte oxidative metabolism with pregnancy compromises the production of TNF and IL-6 in response to MDP but not LPS. Overall, mitochondrially centred metabolic capabilities of late gestation monocytes are downregulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield new therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.

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