Cardiac macrophages undergo dynamic changes after coxsackievirus B3 infection and promote the progression of myocarditis.

Abstract

Although most patients with acute viral myocarditis recover spontaneously, some patients progress to heart failure. Perturbations in innate immunity may partially explain the heterogeneity of clinical outcomes. As the most abundant immune cells in the heart, cardiac macrophages have heterogeneous origins, including embryonic-derived resident macrophages (ResMϕs) and monocyte-derived macrophages (MoMFs). However, the time course change and role of cardiac macrophage subsets has not been fully explored. In the present study, we found that BALB/c mice had prolonged MoMF accumulation and low proportions of ResMϕs that could not be restored to normal levels. MoMFs of BALB/c mice generally exhibit an M1-dominant functional phenotype. Moreover, the preferential depletion of MoMF by a C-C chemokine receptor type 2 (CCR2) inhibitor resulted in improved acute myocarditis and chronic fibrosis, as well as the recovery of ResMϕs number and reduced CD4+ T cell expansion. Hence, immunomodulatory therapy that targets the balance among cardiac macrophages and modulates their function is expected to prevent the progression of cardiac injury to overt heart failure and improve adverse outcomes.