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.
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•CSF1R is a pan MPS marker in humans•CSF1R is stable and can be used as enumeration and isolation tool in human blood and tissues•M1/M2 gene signature modules capture macrophage activation with precision•M1/M2 signature analysis highlights macrophage activation mosaicism
Orsenigo et al. show that CSF1R permits the quantification of human monocytes, macrophages, and dendritic cells. They also propose a modular M1/M2 gene expression tool to assess macrophage activation by IL-4, steroids, IFN, and LPS. Signature analysis highlights kinetics and macrophage activation mosaicism, exemplified by mixed M1/M2 macrophage activation states.