Progressive replacement of embryo-derived cardiac macrophages with age

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Kaaweh Molawi - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Yochai Wolf - , Weizmann Institute of Science (Author)
  • Prashanth K Kandalla - , Marseille-Luminy Immunology Center (CIML), Aix-Marseille Université, INSERM - Institut national de la santé et de la recherche médicale, French National Centre for Scientific Research (CNRS) (Author)
  • Jeremy Favret - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Nora Hagemeyer - , University of Freiburg (Author)
  • Kathrin Frenzel - , University of Freiburg (Author)
  • Alexander R Pinto - , Monash University (Author)
  • Kay Klapproth - , German Cancer Research Center (DKFZ) (Author)
  • Sandrine Henri - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Bernard Malissen - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Hans-Reimer Rodewald - , German Cancer Research Center (DKFZ) (Author)
  • Nadia A Rosenthal - , Monash University (Author)
  • Marc Bajenoff - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Marco Prinz - , University of Freiburg (Author)
  • Steffen Jung - , Weizmann Institute of Science (Author)
  • Michael H Sieweke - , Marseille-Luminy Immunology Center (CIML), Aix-Marseille Université, INSERM - Institut national de la santé et de la recherche médicale, French National Centre for Scientific Research (CNRS), Max Delbrück Center for Molecular Medicine (MDC) (Author)

Abstract

Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1(+) cMΦ diversifies into MHCII(+) and MHCII(-) cells. Genetic fate mapping demonstrated that cMΦ derived from CX3CR1(+) embryonic progenitors persisted into adulthood but the initially high contribution to resident cMΦ declined after birth. Consistent with this, the early significant proliferation rate of resident cMΦ decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMΦ populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMΦ. Together, our observations indicate that in the heart, embryo-derived cMΦ show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.

Details

Original languageEnglish
Pages (from-to)2151-8
Number of pages8
JournalThe Journal of experimental medicine
Volume211
Issue number11
Publication statusPublished - 20 Oct 2014
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC4203946
Scopus 84908227801

Keywords

Keywords

  • Age Factors, Animals, Animals, Newborn, Antigens, Surface/metabolism, Cell Differentiation, Cell Proliferation, Female, Immunophenotyping, Macrophages/cytology, Mice, Mice, Transgenic, Monocytes/cytology, Myocardium/cytology, Phenotype