Role of Toll-like receptor (TLR) in the control of parasitemia and T-cell and parasite densities in the brains of Trypanosoma brucei brucei–infected mice. A, Levels of parasitemia in infected wild-type (WT), Tlr2−/−, Tlr4−/−, Tlr9−/−, and Tlr2/9−/− mice. Each point represents mean log10 parasites per milliliter ± standard error of measurement (SEM) for 4 animals per group. *P < .05 (analysis of variance [ANOVA]; significant differences between WT and Tlr9−/− mice); #P < .05 (ANOVA; significant differences between WT and Tlr2/9−/− mice); ƒP < .05 (ANOVA; significant differences between WT and Tlr4−/− mice ). B–G, Mean number (± SEM) of CD4+ (B, E) and CD8+ (C, F) T cells and T. brucei brucei (D, G) per square millimeter in the corpus callosum (C. callosum) (B–D) and septal nuclei (E–G) of infected WT, Tlr2−/−, Tlr4−/−, Tlr9−/−, and Tlr2/9−/− mice at 27 days post infection (3 or 4 animals per group). *P < .05 (unpaired t test; significantly different from WT mice at same postinfection time point); #P < .05 (unpaired t test; significant differences in T. brucei brucei density compared with tlr2/9−/− mice). H–L, Relative expression of Ifn-γ (H), Cxcl-10 (I), Tnf-α (J), Ifn-β (K), and Cd11b (L) messenger RNA (mRNA) in the brains of uninfected WT controls and WT and Tlr2/9−/− mice at 27 days post infection. Each bar represents the mean ± SEM of values obtained from 4 animals. *P < .05 and **P < .01 (unpaired t test; significantly different from infected WT mice). M, Purified splenic T cells from WT or Tlr2/9−/− mice infected or not infected with T. brucei brucei for 25 days were cocultured with syngeneic bone marrow–derived dendritic cells (DCs) in the presence of T. brucei brucei lysates. Interferon (IFN) γ was assayed by enzyme-linked immunosorbent assay in culture supernatants 72 hours after incubation; mean values (± SEM) from triplicate wells are presented. The experiment shown was performed twice, with similar results. *P < .05 (unpaired t test; significantly different from WT T cells + DCs + antigen).