Eosinophil Deficiency Exacerbates Aberrant Cardiac Repair and Adverse Remodeling After Acute Myocardial Infarction: Insights into Immunological Mechanisms

Myocardial infarction (MI) triggers an acute inflammatory response essential for infarct repair, but dysregulated inflammation can lead to adverse cardiac remodeling and heart failure. This study examined the role of eosinophils in post-MI cardiac repair using clinical data from patients with ST-segment elevation MI (STEMI) and experimental models in mice. In both human STEMI patients and mice following experimental MI, peripheral blood eosinophil counts declined acutely, accompanied by recruitment of activated eosinophils to the infarct zone. Genetic eosinophil deficiency (in ΔdblGATA mice) or pharmacological depletion (via anti-Siglec-F antibody) resulted in exacerbated adverse remodeling, including larger scar size, increased myocardial inflammation, attenuated polarization toward anti-inflammatory/pro-repair macrophages (reduced CD206+ and RELM-α expression), enhanced neutrophil influx, and deterioration of left ventricular structure and function (greater dilation and impaired systolic performance). These detrimental effects were linked to impaired resolution of inflammation and defective scar maturation. Notably, adverse remodeling in eosinophil-deficient mice was rescued by interleukin-4 (IL-4) therapy, suggesting that eosinophil-derived or -influenced IL-4 signaling promotes anti-inflammatory macrophage phenotypes and effective tissue repair. Overall, eosinophils play a protective, non-redundant role in regulating immunological mechanisms during infarct healing by facilitating inflammation resolution, promoting reparative macrophage polarization, and preventing excessive fibrosis and adverse remodeling. These findings highlight eosinophils as potential modulators of post-MI outcomes and suggest therapeutic strategies, such as IL-4 augmentation, for patients with low eosinophil counts at high risk of poor recovery.