title: Progressive replacement of embryo-derived cardiac macrophages with age.
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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Kaaweh
authors.initials: K
authors.lastname: Molawi
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Yochai
authors.initials: Y
authors.lastname: Wolf
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors.forename: Prashanth K
authors.initials: PK
authors.lastname: Kandalla
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Favret
authors.affiliation: Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Hagemeyer
authors.affiliation: Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Frenzel
authors.affiliation: Australian Regenerative Medicine Institute (ARMI), Monash University, Clayton 3800, Victoria, Australia.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Pinto
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Klapproth
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Australian Regenerative Medicine Institute (ARMI), Monash University, Clayton 3800, Victoria, Australia National Heart and Lung Institute, Imperial College London, London SW7 2AZ, England, UK.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Rosenthal
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bajenoff
authors.affiliation: Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79106 Freiburg, Germany Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, Germany sieweke@ciml.univ-mrs.fr.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Sieweke
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D010641:Phenotype
chemical_list: D000954:Antigens, Surface