CCR2 Plays a Protective Role in Rocio Virus–Induced Encephalitis by Promoting Macrophage Infiltration Into the Brain

Rocio virus (ROCV) is a highly neuropathogenic mosquito-transmitted flavivirus responsible for an unprecedented outbreak of human encephalitis during 1975-1976 in Sao Paulo State, Brazil. Previous studies have shown an increased number of inflammatory macrophages into the central nervous system (CNS) of ROCV-infected mice, implying a role for macrophages in the pathogenesis of ROCV. Here, we showed that ROCV infection results in increased expression of C-C chemokine ligand 2 (CCL2) in the blood and in infiltration of macrophages into the brain. Moreover, we showed using C-C chemokine receptor 2 (CCR2) knockout mice that CCR2 expression was essential for macrophage infiltration in the brains during ROCV infection and that the lack of CCR2 resulted in increased disease severity and mortality. Thus, our findings show the protective role of CCR2-mediated infiltration of macrophages in the brain during ROCV infection.