The human heart contains distinct macrophage subsets with divergent origins and functions

Geetika Bajpai, Caralin Schneider, Nicole Wong, Andrea Bredemeyer, Maarten Hulsmans, Matthias Nahrendorf, Slava Epelman, Daniel Kreisel, Yongjian Liu, Akinobu Itoh, Thirupura S. Shankar, Craig H. Selzman, Stavros G. Drakos, Kory J. Lavine

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1234-1245
Number of pages12
JournalNature medicine
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Dive into the research topics of 'The human heart contains distinct macrophage subsets with divergent origins and functions'. Together they form a unique fingerprint.

Cite this