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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2014-01, Vol.40 (1), p.91-104
Main Authors: Epelman, Slava, Lavine, Kory J., Beaudin, Anna E., Sojka, Dorothy K., Carrero, Javier A., Calderon, Boris, Brija, Thaddeus, Gautier, Emmanuel L., Ivanov, Stoyan, Satpathy, Ansuman T., Schilling, Joel D., Schwendener, Reto, Sergin, Ismail, Razani, Babak, Forsberg, E. Camilla, Yokoyama, Wayne M., Unanue, Emil R., Colonna, Marco, Randolph, Gwendalyn J., Mann, Douglas L.
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens, Ly
Antigens, Ly - metabolism
Cardiomyocytes
Cell Death
Cell Differentiation
Cell Lineage
Cells, Cultured
Fetal Development
Heart
Heart - embryology
Heart attacks
Homeostasis
Life Sciences
Macrophages
Macrophages - immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Monocytes
Monocytes - physiology
Myocarditis
Myocarditis - immunology
Myocardium
Myocardium - immunology
Myocytes, Cardiac
Myocytes, Cardiac - immunology
Phagocytosis
Prenatal development
Receptors, CCR2
Receptors, CCR2 - metabolism
Rodents
Studies
Transcription factors
Transcriptome
Yolk Sac
Yolk Sac - cytology
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Summary: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, Ly6chi 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. •Yolk-sac and fetal monocyte progenitors give rise to adult cardiac macrophages•Yolk-sac macrophages persisted into adulthood only in the heart, liver, and brain•Embryonically established resident macrophages can be replaced by blood monocytes•Cardiac macrophages differentially activate T cells and take up dying cardiomyocytes
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2013.11.019