FIG 4.

Tamoxifen-treated Cxcr2-CKO mice are susceptible to JHMV-induced neuroinflammation. Cxcr2-CKO mice were treated with either tamoxifen (n = 22) or vehicle (n = 10), rested for 2 weeks, and infected i.c. with 250 PFU of JHMV. The data are representative of those from 3 independent experiments. (A) Clinical disease developed in both groups, and vehicle-treated Cxcr2-CKO mice had worse (P < 0.05) disease at 12 days p.i. than control mice, but otherwise, there were no statistically significant differences in disease severity or mortality out to day 28 p.i. between the experimental groups. (B) Viral titers in the brains and spinal cords of tamoxifen- and vehicle-treated mice at days 5, 7, and 10 p.i. *, P < 0.05. By day 21 p.i., virus was not detected (ND) in the brains of experimental mice. dpi, day postinfection. (C) No differences in the frequencies of virus-specific CD4⁺ and CD8⁺ T cells were detected, as determined by tetramer staining at day 7 p.i. (D) At day 7 p.i., similar numbers of neutrophils (Neut.), macrophages (Mac.), and T cells were detected in the brains of JHMV-infected Cxcr2-CKO mice treated with either vehicle or tamoxifen. Day 7 p.i. flow cytometric data were derived from 2 independent experiments with a minimum of 3 mice per group for each experiment. (E) RNA analysis revealed no changes in proinflammatory gene expression within the brains of the experimental groups at day 7 p.i. The data represent the average for 2 mice per group.