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.

中文翻译：

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人类心脏包含具有不同起源和功能的不同巨噬细胞亚群。


小鼠的范式转变研究已确定组织巨噬细胞异质性是免疫反应的关键决定因素。相比之下，令人惊讶的是，人们对人类巨噬细胞异质性知之甚少。小鼠心脏内的巨噬细胞分为 CCR2- 和 CCR2+ 亚群，具有不同的起源、再增殖机制和功能。在这里，我们证明人类心肌还含有不同的 CCR2- 和 CCR2+ 巨噬细胞亚群。对性别不匹配的心脏移植受者的分析表明，CCR2-巨噬细胞是一种组织驻留群体，专门通过局部增殖来补充，而CCR2+巨噬细胞则通过单核细胞募集和增殖来维持。此外，CCR2-和CCR2+巨噬细胞具有不同的功能特性，类似于小鼠心脏中的修复性CCR2-和炎症性CCR2+巨噬细胞。临床上，CCR2+巨噬细胞丰度与心力衰竭患者的左心室重构和收缩功能相关。总的来说，这些观察结果为人类心脏中巨噬细胞异质性的功能重要性提供了初步证据。