Host-parasite interaction in latent cerebral toxoplasmosis: The role of cytokine response in a mouse model.

BACKGROUND: Toxoplasma gondii is a widespread intracellular protozoan that can cause chronic infection in immunocompetent hosts, leading to subclinical neuroinflammation. Understanding the immunopathogenesis of chronic cerebral toxoplasmosis requires well-characterized animal models. AIM: This study aimed to evaluate infection severity, affected immune cell populations, and cytokine response in both early and late chronic phases of T. gondii infection. METHODS: A murine model was developed by infecting C57BL/6 mice with a sub-infective dose (104 tachyzoites) of the ME49 strain. Forty mice were used: 30 infected and 10 controls. Animals were sacrificed on days 30, 60, and 180 after infection. Brains were analyzed using histopathology, immunohistochemistry, and nested polymerase chain reaction (PCR). RESULTS: Histopathological changes, including gliosis, meningitis, vasculitis, and neuronal degeneration, were most prominent on days 30 and 60 and decreased by day 180. Immunohistochemistry revealed dynamic changes in immune cell populations (CD4(+), CD8(+), CD11b(+), CD11c(+), CD19(+), and FOXP3(+)) and cytokine expression (TNF-α, IFN-γ, IL-1β, IL-4, IL-10, IL-12, and IL-18). A mixed pro- and anti-inflammatory response was observed, shifting toward immunoregulation at day 180, with increased FOXP3(+) cells and anti-inflammatory cytokines. PCR confirmed T. gondii DNA in all infected groups. CONCLUSION: This model shares several immunopathological features with chronic cerebral toxoplasmosis observed in immunocompetent humans, modeling aspects of the infection even in the absence of demonstrable tissue cysts. The immunological shift from pro-inflammatory to regulatory responses highlights the mechanisms of immune modulation and persistence. This study provides a useful platform to explore host-pathogen interactions and CNS immune dynamics in chronic cerebral toxoplasmosis.