title: Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice.
abstract: The paradigm that macrophages that reside in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using fate-mapping models and monocytopenic mice, together with bone marrow chimera and parabiotic models, we found that embryonic precursor cells seeded the intestinal mucosa and demonstrated extensive in situ proliferation during the neonatal period. However, these cells did not persist in the intestine of adult mice. Instead, they were replaced around the time of weaning by the chemokine receptor CCR2-dependent influx of Ly6C(hi) monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, G12 8TA, Scotland, UK.
authors.forename: Calum C
authors.initials: CC
authors.lastname: Bain
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, G12 8TA, Scotland, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bravo-Blas
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, G12 8TA, Scotland, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), New Hunt's House, King's College London, Great Maze Pond, London SE1 1UL, UK.|Peter Gorer Department of Immunobiology, King's College London, London SE1 9RT, UK.
authors.forename: Elisa Gomez
authors.initials: EG
authors.lastname: Perdiguero
authors.affiliation: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), New Hunt's House, King's College London, Great Maze Pond, London SE1 1UL, UK.|Peter Gorer Department of Immunobiology, King's College London, London SE1 9RT, UK.
authors.forename: Frederic
authors.initials: F
authors.lastname: Geissmann
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Universite, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Universite, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Osborne
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.|Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: David
authors.initials: D
authors.lastname: Artis
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, G12 8TA, Scotland, UK.
authors.forename: Allan McI
authors.initials: AM
authors.lastname: Mowat
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010227:Parabiosis; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D000950:Antigens, Ly; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C036763:monocyte-macrophage differentiation antigen