Predominant IFN-γ-mediated expression of CXCL9, CXCL10, and CCL5 proteins in the brain during chronic infection with Toxoplasma gondii in BALB/c mice resistant to development of toxoplasmic encephalitis (40.21)

Abstract We examined the role of IFN-γ in expression of chemokine mRNA and proteins in the brain during chronic infection with Toxoplasma gondii using BALB/c and BALB/c-background IFN-γ knockout (IFN-γ-/-) mice. BALB/c mice are genetically resistant to development of toxoplasmic encephalitis and establish a latent, chronic infection in the brain through IFN-γ-mediated immune responses. Amounts of mRNA for CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL5 significantly increased in the brains of wild-type mice after infection. CXCL9, CXCL10, and CCL5 mRNA were most abundant among these chemokines. An increase in amounts of mRNA for CXCL10, CCL2, CCL3, and CCL5 was also observed in the brains of IFN-γ-/- mice after infection, although CXCL10 and CCL5 mRNA levels in infected IFN-γ-/- mice were significantly lower than those of infected wild-type animals. Amounts of mRNA for CXCL9 and CXCL11 remained at the basal levels in infected IFN-γ-/- mice. When amounts of the chemokine proteins were examined in the brain homogenates of uninfected and infected mice of both strains, large amounts of CXCL9, CXCL10, and CCL5 were detected only in infected wild-type animals. These results indicate that CXCL9, CXCL10, and CCL5 are the chemokines predominantly induced in the brains of genetically resistant BALB/c mice during chronic infection with T. gondii, and their expression is dependent on IFN-γ.