Unifying considerations and evidence of macrophage activation mosaicism through human CSF1R and M1/M2 genes
Federica Orsenigo,
Alexander Stewart,
Clare P. Hammer,
Emma Clarke,
Daniel Simpkin,
Hossameldin Attia,
Timothy Rockall,
Siamon Gordon,
Fernando O. Martinez
Affiliations
Federica Orsenigo
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK
Alexander Stewart
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK; Virology Department, Animal and Plant Health Agency, APHA-Weybridge, KT15 3NB Addlestone, UK
Clare P. Hammer
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK; Royal Surrey County Hospital NHS Foundation Trust, GU2 7XX Guildford, UK
Emma Clarke
Royal Surrey County Hospital NHS Foundation Trust, GU2 7XX Guildford, UK
Daniel Simpkin
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK
Hossameldin Attia
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK; Royal Surrey County Hospital NHS Foundation Trust, GU2 7XX Guildford, UK
Timothy Rockall
Royal Surrey County Hospital NHS Foundation Trust, GU2 7XX Guildford, UK
Siamon Gordon
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan; Sir William Dunn School of Pathology, University of Oxford, OX13RE Oxford, UK
Fernando O. Martinez
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, UK; Corresponding author
Summary: 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.
