Abundant Neutrophil-Initiated Acute Myocardial Injury Following Coxsackievirus A6 Infection

Coxsackievirus A6 (CVA6) is currently considered as a predominant pathogen of hand, foot, and mouth disease (HFMD), and is occasionally linked to myocardial injury. We first established a mouse model of CVA6-induced myocardial injury. Next, we analyzed the immune cell phenotypes CVA6-infected mice hearts by fluorescence-activated cell sorting, and found that CVA6 led to massive neutrophils infiltration, suggesting their potential link with the occurrence of myocardial injury. We further used either alpha Gr-1 or alpha Ly6G antibody to deplete neutrophils, and found that neutrophil-depleted animals showed decreased cardiac enzymes, lower degree of pathology in hearts, and reduced inflammatory cytokine production compared to isotype controls. Finally, we confirmed the involvement of neutrophils in myocardial injury of clinical patients with severe HFMD. Our study suggests that excessive neutrophils contribute to myocardial injury caused by CVA6 infection, which provides new insights into myocardial injury during the development of HFMD severity and the outcome of immune cell-mediated therapies.

Automated summary

Coxsackievirus A6 (CVA6) infection is associated with myocardial injury in hand, foot, and mouth disease (HFMD). Neutrophil infiltration is linked to the occurrence of myocardial injury. Depletion of neutrophils reduces cardiac enzymes, pathology in the heart, and inflammatory cytokine production. Clinical observations also support the role of neutrophils in myocardial injury.