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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)929-937
Number of pages9
JournalNature Immunology
Volume15
Issue number10
Early online date24 Aug 2014
DOIs
Publication statusPublished - Oct 2014

Keywords

  • Animals
  • Animals, Newborn
  • Antigens, CD11b
  • Antigens, Differentiation
  • Antigens, Ly
  • Bone Marrow Transplantation
  • Cell Differentiation
  • Cell Proliferation
  • Flow Cytometry
  • Gene Expression
  • Intestinal Mucosa
  • Intestines
  • Macrophages
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Monocytes
  • Parabiosis
  • Receptors, CCR2
  • Receptors, Chemokine
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

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