Immune cell dynamics in myocardial infarction: mechanisms, therapeutic targets, and translational Perspectives

Myocardial infarction (MI) triggers a complex and dynamic immune response involving both innate and adaptive immune cells. Among these, macrophages (Mφ), neutrophils, dendritic cells, and mast cells play essential roles in inflammation, tissue repair, and cardiac remodeling. Although inflammation is necessary for clearing necrotic tissue, dysregulated immune responses can exacerbate injury and lead to adverse cardiac outcomes. A comprehensive understanding of immune cell heterogeneity and functions in MI is critical for developing targeted therapeutic strategies.

This review aims to systematically summarize the origins, phenotypic diversity, and functional roles of major immune cell populations involved in MI, with a particular focus on Mφs and neutrophils. It further seeks to evaluate emerging therapeutic strategies targeting these immune cells to improve cardiac repair and clinical outcomes following MI.

Recent advances highlight the remarkable heterogeneity and plasticity of cardiac immune cells. Mφs, derived from both resident and monocyte-origin populations, exhibit dynamic phenotypic transitions across inflammatory, proliferative, and reparative phases of MI. CCR2⁺ Mφs primarily drive inflammation, whereas CCR2⁻ subsets contribute to tissue repair and angiogenesis. Neutrophils, as early responders, not only mediate acute inflammation through degranulation and neutrophil extracellular trap formation but also participate in resolution and remodeling processes. Importantly, emerging evidence challenges the traditional dichotomy of pro- and anti-inflammatory phases, revealing overlapping and context-dependent immune functions. Novel therapeutic approaches, including modulation of Mφ polarization, inhibition of excessive neutrophil activation, and targeting specific signaling pathways (e.g., C-C motif chemokine receptor type 2/ligand type 2 (CCR2/CCL2), NOD-like receptor family pyrin domain containing 3 (NLRP3)), demonstrate promising preclinical and clinical potential. Collectively, these findings underscore the importance of precise immune modulation rather than broad immunosuppression in MI treatment, paving the way for more effective and personalized therapeutic strategies.