Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice

Calum C Bain; Alberto Bravo-Blas; Charlotte L Scott; Elisa Gomez Perdiguero; Frederic Geissmann; Sandrine Henri; Bernard Malissen; Lisa C Osborne; David Artis; Allan McI Mowat

doi:10.1038/ni.2967

Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice

Nat Immunol. 2014 Oct;15(10):929-937. doi: 10.1038/ni.2967. Epub 2014 Aug 24.

Authors

Calum C Bain^#¹, Alberto Bravo-Blas^#¹, Charlotte L Scott¹, Elisa Gomez Perdiguero^{2

3}, Frederic Geissmann^{2

3}, Sandrine Henri^{4

5

6}, Bernard Malissen^{4

5

6}, Lisa C Osborne⁷, David Artis^{7

8}, Allan McI Mowat¹

Affiliations

¹ Institute of Infection, Immunity and Inflammation, College of Veterinary, Medical and Life Science, University of Glasgow, G12 8TA, Scotland, UK.
² Centre for Molecular and Cellular Biology of Inflammation (CMCBI), New Hunt's House, King's College London, Great Maze Pond, London SE1 1UL, UK.
³ Peter Gorer Department of Immunobiology, King's College London, London SE1 9RT, UK.
⁴ Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Universite, Marseille, France.
⁵ INSERM U1104, Marseille, France.
⁶ CNRS UMR7280, Marseille, France.
⁷ Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁸ Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

^# Contributed equally.

PMID: 25151491
PMCID: PMC4169290
DOI: 10.1038/ni.2967

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Antigens, Differentiation / genetics
Antigens, Differentiation / immunology
Antigens, Differentiation / metabolism
Antigens, Ly / immunology
Antigens, Ly / metabolism
Bone Marrow Transplantation
CD11b Antigen / genetics
CD11b Antigen / immunology
CD11b Antigen / metabolism
CX3C Chemokine Receptor 1
Cell Differentiation / immunology
Cell Proliferation
Flow Cytometry
Gene Expression / immunology
Intestinal Mucosa / cytology
Intestinal Mucosa / immunology*
Intestinal Mucosa / metabolism
Intestines / cytology
Intestines / immunology*
Macrophages / immunology*
Macrophages / metabolism
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Models, Immunological
Monocytes / immunology*
Monocytes / metabolism
Parabiosis
Receptors, CCR2 / genetics
Receptors, CCR2 / immunology
Receptors, CCR2 / metabolism
Receptors, Chemokine / genetics
Receptors, Chemokine / immunology
Receptors, Chemokine / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors

Substances

Antigens, Differentiation
Antigens, Ly
CD11b Antigen
CX3C Chemokine Receptor 1
Cx3cr1 protein, mouse
Ly-6C antigen, mouse
Receptors, CCR2
Receptors, Chemokine
monocyte-macrophage differentiation antigen

Abstract

Publication types

MeSH terms

Substances

Grants and funding