Comparison of dynamic expressions of Tim-3 and PD-1 in the brains between toxoplasmic encephalitis-resistant BALB/c and -susceptible C57BL/6 mice.

T cells and IFN-γ are essential for controlling the reactivation of toxoplasmic encephalitis (TE), regardless of whether mice are susceptible or resistant to TE. It has been demonstrated that CD8(+) T cells exhausted in chronic Toxoplasma gondii infection result in TE reactivation in C57BL/6 mice. However, this phenomenon had not been reported in genetically TE-resistant BALB/c mice. To explore the immune mechanism of TE in different backgrounds of mice, the dynamic expressions of Tim-3, programmed cell death 1 (PD-1), and their ligands (galectin-9, PD-L1, PD-L2) in brain tissues were compared between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Prugniaud (Pru, a type II strain) of T. gondii in this study. Compared with infected BALB/c mice, there were remarkable pathological changes with significantly higher histological scores in the brains of C57BL/6 mice at 14, 35, 50, and 70 days postinfection (p.i., P < 0.01); significantly increased mRNA expressions of Tim-3 at 35 (P < 0.05) and 70 (P < 0.01) days p.i.; and significantly increased PD-1 at all the times p.i. (P < 0.01) in the brains of infected C57BL/6 mice. Furthermore, there were significantly increased mRNA expressions of PD-L1 in the brain of C57BL/6 mice than that in BALB/c mice at all the times p.i. (P < 0.01). Although the mRNA expressions of galectin-9 (ligand of Tim-3) were increased in the brains of both lineages of mice at all the times p.i., it showed no differences between the two lineages of mice. Our data suggest that the differences of Tim-3 and PD-1/PD-L1 expressions may contribute to the different immune responses between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Pru strain of T. gondii.