Journal
NATURE MEDICINE
Volume 24, Issue 8, Pages 1234-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-018-0059-x
Keywords
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Funding
- Children's Discovery Institute of Washington University and St. Louis Children's Hospital [CH-II-2015-462, CH-II-2017-628]
- Foundation for Barnes-Jewish Hospital [8038-88]
- NHLBI [R01 HL138466, R01 HL139714, R01 HL135121-01]
- National Institutes of Health (NIH) [K08 HL123519]
- Burroughs Welcome Fund [1014782]
- NCI [P30 CA91842]
- ICTS/CTSA Grant from the National Center for Research Resources (NCRR), a component of the NIH [UL1TR000448]
- NIH Roadmap for Medical Research
- AHA [HF 16SFRN29020000]
- Nora Eccles Treadwell Foundation
- NIH [HL139598, R01HL131908, R01HL125655, P01AI116501, R01 HL094601]
- MGH Research Scholar Program
- Veterans Administration Merit Review grant [1I01BX002730]
- Foundation for Barnes-Jewish Hospital
- MGH ECOR Tosteson
- Fund for Medical Discovery Fellowship [2017A052660]
- [P30 DK52574]
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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.
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