Unifying considerations and evidence of macrophage activation mosaicism through human CSF1R and M1/M2 genes

Cell Rep. 2024 Jun 25;43(6):114352. doi: 10.1016/j.celrep.2024.114352. Epub 2024 Jun 12.

Abstract

Addressing the mononuclear phagocyte system (MPS) and macrophage M1/M2 activation is important in diagnosing hematological disorders and inflammatory pathologies and designing therapeutic tools. CSF1R is a reliable marker to identify all circulating MPS cells and tissue macrophages in humans using a single surface protein. CSF1R permits the quantification and isolation of monocyte and dendritic cell (DC) subsets in conjunction with CD14, CD16, and CD1c and is stable across the lifespan and sexes in the absence of overt pathology. Beyond cell detection, measuring M1/M2 activation in humans poses challenges due to response heterogeneity, transient signaling, and multiple regulation steps for transcripts and proteins. MPS cells respond in a conserved manner to M1/M2 pathways such as interleukin-4 (IL-4), steroids, interferon-γ (IFNγ), and lipopolysaccharide (LPS), for which we propose an ad hoc modular gene expression tool. Signature analysis highlights macrophage activation mosaicism in experimental samples, an emerging concept that points to mixed macrophage activation states in pathology.

Keywords: CP: Immunology; CSF1R; IFNg; IL-4; LPS; M1 M2 activation; dexamethasone; macrophages; monocytes; mononuclear phagocyte system; steroids.

MeSH terms

  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Glycoproteins
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation* / genetics
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Male
  • Monocytes / metabolism
  • Mononuclear Phagocyte System / metabolism
  • Mosaicism
  • Receptor, Macrophage Colony-Stimulating Factor
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor* / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor* / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism

Substances

  • CSF1R protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Interferon-gamma
  • Lipopolysaccharides
  • Lipopolysaccharide Receptors
  • Interleukin-4
  • Receptors, IgG
  • Antigens, CD1
  • CD1C protein, human
  • Glycoproteins
  • Receptor, Macrophage Colony-Stimulating Factor