TY - JOUR
T1 - The human heart contains distinct macrophage subsets with divergent origins and functions
AU - Bajpai, Geetika
AU - Schneider, Caralin
AU - Wong, Nicole
AU - Bredemeyer, Andrea
AU - Hulsmans, Maarten
AU - Nahrendorf, Matthias
AU - Epelman, Slava
AU - Kreisel, Daniel
AU - Liu, Yongjian
AU - Itoh, Akinobu
AU - Shankar, Thirupura S.
AU - Selzman, Craig H.
AU - Drakos, Stavros G.
AU - Lavine, Kory J.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2− and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2− and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2− macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2− and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2− and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.
AB - Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2− and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2− and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2− macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2− and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2− and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.
UR - http://www.scopus.com/inward/record.url?scp=85048281756&partnerID=8YFLogxK
U2 - 10.1038/s41591-018-0059-x
DO - 10.1038/s41591-018-0059-x
M3 - Article
C2 - 29892064
AN - SCOPUS:85048281756
SN - 1078-8956
VL - 24
SP - 1234
EP - 1245
JO - Nature medicine
JF - Nature medicine
IS - 8
ER -