Macrophages play a crucial role in protection against rJHMV-induced encephalitis in Lyz2-DP1−/− mice. (a to c) Infected Lyz2-DP1−/− mice were treated with anti-CCR2 (MC21) or control antibody at −1, 3, and 7 dpi and monitored for survival, weight, and clinical score. MC21 mAb treatment resulted in a marked increase in disease severity in Lyz-DP1−/− mice. A log rank Mantel-Cox test was used to analyze survival (**, P < 0.01 [control and anti-CCR2 mAb-treated mice]). Mann-Whitney U tests were used to analyze weight (days 7 to 11) (P < 0.05) (b) and clinical score (days 7 to 11) (P < 0.05) (c) data. (d) Virus titers in the brain were elevated in MC21- compared to IgG-treated mice. (e) Flow cytometric analysis showing decreased MHC-II frequencies in MC21 mAb-treated Lyz2-DP1−/− mice. (f) Bar graph showing frequencies of MHC-II-positive microglia. (g) Flow cytometry data showing that MC21 antibody treatment affects macrophage but not neutrophil entry into the CNS. (h) Summary data. Data were analyzed by Mann-Whitney U tests. **, P < 0.01; ****, P < 0.0001.