Blocking CCL3-mediated neutrophil recruitment into the brain alleviates immunopathology following severe enterovirus 71 infection

Summary: Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients. Inhibition of CCL3 by anti-CCL3 antibodies or selected miRNAs significantly reduces the neutrophils infiltration in brains and the mortality of EV71-infected mice. Collectively, CCL3-mediated neutrophils recruitment into the brain contributes to the severe immunopathology of EV71 infection, which provides a potential diagnostic and therapeutic target for EV71 infection.