Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation

Nat Immunol. 2017 Jun;18(6):642-653. doi: 10.1038/ni.3734. Epub 2017 Apr 24.

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

  • Animals
  • Antigens, Differentiation / metabolism
  • Flow Cytometry
  • Granuloma / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Interleukin-4 / immunology
  • Lectins, C-Type / metabolism
  • Liver / immunology*
  • Liver / pathology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Peritoneal Cavity / cytology
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / metabolism
  • Schistosoma mansoni
  • Schistosomiasis mansoni / immunology*
  • Schistosomiasis mansoni / pathology
  • Tretinoin / pharmacology
  • Uncoupling Protein 1 / metabolism
  • Vitamin A Deficiency / immunology*
  • Vitamins / pharmacology

Substances

  • Antigens, Differentiation
  • Histocompatibility Antigens Class II
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Pdcd1lg2 protein, mouse
  • Programmed Cell Death 1 Ligand 2 Protein
  • Receptors, Cell Surface
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Vitamins
  • monocyte-macrophage differentiation antigen
  • Interleukin-4
  • Tretinoin