Article | Published:

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

Nature Immunology volume 15, pages 929937 (2014) | Download Citation

  • A Corrigendum to this article was published on 20 October 2014

This article has been updated

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 Ly6Chi 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.

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Change history

  • 08 September 2014

    In the version of this article initially published online, the vertical axis of the bottom right graph in Figure 3h was incorrect. It should read "F4/80loCD11b+ cells (×105)." Also, in the Online Methods, the first sentence of the third subsection ("Generation of bone marrow chimeras") identifies the donor mice incorrectly. It should read "...BM cells from CD45.2+ wild-type mice and CD45.1+ Ccr2-/- mice...." The errors have been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank D. Vaughan for help with flow cytometry; B. McColl (Roslin Institute, Edinburgh) for the CCR2-reporter mice; and V. Cerovic for critical reading of the manuscript. Supported by The Wellcome Trust (C.C.B., A.M.M. and C.L.S.), the Medical Research Council UK (C.C.B., A.M.M. and C.L.S.), Conacyt (A.B.-B.), Tenovus Scotland (A.B.-B.), the EE-ASI European Collaborative Research Project (S.H. and B.M.) and the Agence National de Recherche (S.H. and B.M.).

Author information

Author notes

    • Calum C Bain
    •  & Alberto Bravo-Blas

    These authors contributed equally to this work.

    • Calum C Bain
    •  & Charlotte L Scott

    Present addresses: MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK (C.C.B.), and VIB Ghent University, Inflammation Research Centre, Laboratory of Immunoregulation, Ghent, Belgium (C.L.S.).

Affiliations

  1. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, Scotland, UK.

    • Calum C Bain
    • , Alberto Bravo-Blas
    • , Charlotte L Scott
    •  & Allan McI Mowat
  2. Centre for Molecular and Cellular Biology of Inflammation, New Hunt's House, King's College London, London, UK.

    • Elisa Gomez Perdiguero
    •  & Frederic Geissmann
  3. Peter Gorer Department of Immunobiology, King's College London, London, UK.

    • Elisa Gomez Perdiguero
    •  & Frederic Geissmann
  4. Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Marseille, France.

    • Sandrine Henri
    •  & Bernard Malissen
  5. INSERM U1104, Marseille, France.

    • Sandrine Henri
    •  & Bernard Malissen
  6. CNRS UMR7280, Marseille, France.

    • Sandrine Henri
    •  & Bernard Malissen
  7. Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Lisa C Osborne
    •  & David Artis
  8. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • David Artis

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Contributions

C.C.B. designed, performed and analyzed experiments and wrote the manuscript; A.B.-B. designed, performed and analyzed experiments; C.L.S. performed experiments; E.G.P., F.G., S.H., B.M., L.C.O. and D.A. provided mice and reagents; and A.M.M. designed and supervised the studies and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Allan McI Mowat.

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DOI

https://doi.org/10.1038/ni.2967

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