Immune modulation and evasion by Toxoplasma gondii: Roles of IFN-γ, TNF-α, IL-10, and IgM in murine infection.

Toxoplasma gondii persists lifelong in the host by manipulating the balance between protective T helper type 1 (Th1) immunity and regulatory pathways that limit immunopathology. Among these regulators, interleukin-10 (IL-10) is proposed to be a pivotal suppressor of anti-parasite immunity, yet its precise functional contribution during chronic toxoplasmosis remains incompletely defined. This study dissected the immunoregulatory role of IL-10 during experimental T. gondii infection by integrating analyses of brain cyst kinetics, systemic cytokine dynamics, humoral responses, correlation networks, and tissue pathology. The study included 45 female Swiss albino mice, divided in three equal groups (G), G1 non-infected; G2, T. gondii-infected mice; and G3, T. gondii-infected mice and treated with anti-IL-10 monoclonal antibody. Mice were infected intraperitoneally with 10 ME49 cysts and G3 were treated with anti-IL-10 mAb starting one-week post-infection. Mice were sacrificed at 14-, 28-, and 42-days post-infection for brain cyst counting, liver and brain histopathology, and measurement of serum IFN-γ, TNF-α, IL-10, and IgM by ELISA. Infection induced robust elevations of IFN-γ and TNF-α, confirming a dominant Th1 response essential for early parasite control. IL-10 level increased concurrently, indicating activation of a compensatory regulatory axis. IL-10 neutralization dramatically reshaped disease outcomes: anti-IL-10-treated mice exhibited significantly reduced cerebral cyst burdens and heightened IgM levels, accompanied by pronounced amplification of IFN-γ and TNF-α response. Network analysis revealed strong positive coupling between IFN-γ and TNF-α, while IL-10 displayed marked negative correlations with both cytokines, identifying IL-10 as a master suppressor of inflammatory immunity. However, IL-10 blockades resulted in severe hepatic and neural tissue damage, demonstrating the cost of unrestrained inflammation. IL-10 mediates a crucial balance in toxoplasmosis by suppressing protective Th1 immunity to allow parasite persistence while preventing lethal immunopathology, highlighting its potential as a therapeutic target in severe or reactivated disease.