Specialized functions of resident macrophages in brain and heart

The functions of macrophages in healthy tissues extend beyond their well-established roles as immune sentinels and effectors. Among tissues, cells of the brain and heart possess unique excitatory properties that likely demand special support. Accordingly, existing evidence demonstrates that microglia in the brain has an active role in synaptic organization, control of neuronal excitability, phagocytic removal of debris, and trophic support during brain development. In the heart, recent studies suggest that cardiac macrophages are involved in the regulation of heart homeostasis by phagocytosis, production of trophic, and immune-related factors, and by forming direct contacts with cardiomyocytes to regulate electrical conduction. In this review, we discuss mechanisms associated with the high degree of specialization of resident macrophages in both tissues, their origin and heterogeneity, and their contributions in regulating homeostasis under steady-state and pathological conditions.