Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation.
Cardiac macrophages are crucial for tissue repair after cardiac injury but are not well characterized. Here we identify four populations of cardiac macrophages. At steady state, resident macrophages were primarily maintained through local proliferation. However, after macrophage depletion or during cardiac inflammation, Ly6c(hi) monocytes contributed to all four macrophage populations, whereas resident macrophages also expanded numerically through proliferation. Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave rise to the majority of cardiac macrophages, and the heart was among a minority of organs in which substantial numbers of yolk-sac macrophages persisted in adulthood. CCR2 expression and dependence distinguished cardiac macrophages of adult monocyte versus embryonic origin. Transcriptional and functional data revealed that monocyte-derived macrophages coordinate cardiac inflammation, while playing redundant but lesser roles in antigen sampling and efferocytosis. These data highlight the presence of multiple cardiac macrophage subsets, with different functions, origins, and strategies to regulate compartment size.
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Slava
S
Epelman
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kory J
KJ
Lavine
Department of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Anna E
AE
Beaudin
Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dorothy K
DK
Sojka
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Javier A
JA
Carrero
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Boris
B
Calderon
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Thaddeus
T
Brija
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Emmanuel L
EL
Gautier
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Stoyan
S
Ivanov
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ansuman T
AT
Satpathy
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Joel D
JD
Schilling
Institute of Molecular Cancer Research, University Zurich, CH-8057 Zurich, Switzerland.
Reto
R
Schwendener
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ismail
I
Sergin
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Babak
B
Razani
Department of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
E Camilla
EC
Forsberg
Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wayne M
WM
Yokoyama
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Emil R
ER
Unanue
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Marco
M
Colonna
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gwendalyn J
GJ
Randolph
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: dmann@dom.wustl.edu.
Douglas L
DL
Mann
D000818:Animals; D017951:Antigen Presentation; D000950:Antigens, Ly / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D047109:Fetal Development; D006321:Heart / Q000196:embryology; D006706:Homeostasis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000502:physiology*; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000276:immunology; D010587:Phagocytosis; D054390:Receptors, CCR2 / Q000378:metabolism; D059467:Transcriptome; D015017:Yolk Sac / Q000166:cytology
D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2