Abstract
It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206-PD-L2-MHCII-UCP1+ phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206- macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A-deficient mice infected with S. mansoni had disrupted liver granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80intCD206+ phenotype to F4/80hiCD206- may lead to dysregulated inflammation during helminth infection.
MeSH terms
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Animals
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Antigens, Differentiation / metabolism
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Flow Cytometry
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Granuloma / immunology*
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Histocompatibility Antigens Class II / metabolism
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Interleukin-4 / immunology
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Lectins, C-Type / metabolism
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Liver / immunology*
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Liver / pathology
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / metabolism
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Macrophages, Alveolar / drug effects
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Macrophages, Alveolar / immunology
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Macrophages, Alveolar / metabolism
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Mannose Receptor
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Mannose-Binding Lectins / metabolism
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Mice
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Peritoneal Cavity / cytology
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Programmed Cell Death 1 Ligand 2 Protein / metabolism
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Real-Time Polymerase Chain Reaction
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Receptors, Cell Surface / metabolism
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Schistosoma mansoni
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Schistosomiasis mansoni / immunology*
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Schistosomiasis mansoni / pathology
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Tretinoin / pharmacology
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Uncoupling Protein 1 / metabolism
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Vitamin A Deficiency / immunology*
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Vitamins / pharmacology
Substances
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Antigens, Differentiation
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Histocompatibility Antigens Class II
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Lectins, C-Type
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Mannose Receptor
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Mannose-Binding Lectins
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Pdcd1lg2 protein, mouse
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Programmed Cell Death 1 Ligand 2 Protein
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Receptors, Cell Surface
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Ucp1 protein, mouse
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Uncoupling Protein 1
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Vitamins
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monocyte-macrophage differentiation antigen
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Interleukin-4
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Tretinoin