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

Amarilla, Alberto A; Santos-Junior, Nilton Nascimento; Figueiredo, Mario Luis; Luiz, Joao Paulo Mesquita; Fumagalli, Marcilio Jorge; Colón, David F; Lippi, Veronica; Alfonso, Helda Liz; Lima-Junior, Djalma S; Trabuco, Amanda C; Spinieli, Richard L; Desidera, Amanda C; Leite-Panissi, Christie R A; Lauretti, Flávio; Mendoza, Silvia Elena Sánchez; Silva, Cleide Lúcia Araújo; Rego, Eduardo Magalhaes; Galvao-Lima, Leonardo J; Bassi, Gabriel S; Penharvel Martíns, Sandra L B; Manrique, Wilson Gomez; Alves-Filho, José Carlos; Cunha, Fernando Q; Peng, Nias Y G; Modhiran, Naphak; Setoh, Yin Xiang; Khromykh, Alexander A; Figueiredo, Luiz T M; Aquino, Victor H

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 in the central nervous system (CNS) of ROCV-infected mice, implying a role for macrophages in the pathogenesis of ROCV. Here, we show that ROCV infection results in increased expression of CCL2 in the blood and in infiltration of macrophages into the brain. Moreover, we show, using CCR2 knockout mice, that CCR2 expression is essential for macrophage infiltration in the brain during ROCV infection and that the lack of CCR2 results 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.