Reduction of regulatory T cells during acute Toxoplasma gondii infection is caused by IFN-γ (MPF2P.759)

Abstract

Abstract Toxoplasmosis is an infection disease caused by the protozoan parasite Toxoplasma gondii. A TH1 immune response is essential for protection against the parasite, IFN-γ being the major mediator of resistance. CD4+Foxp3+ Regulatory T cells (Treg) maintain immune homeostasis by actively suppressing pathological and physiological immune responses. Intraperitoneal infection of BALB/c mice with T. gondii cysts leads to high mortality rate and exacerbated IFN-γ levels in sera both of which parallel a decreased Treg number in blood and spleen. Since we observed an inverse correlation between high IFN-γ levels and low Treg cell number in infected mice, we analyzed if this cytokine was involved in Treg reduction. Since STAT-1 is involved during signaling by IFN-γ, we infected STAT-1-/- KO mice with T. gondii and found that the Treg cell number was unchanged in blood and increased in spleen, although all mice died; IFN-γ levels in sera in these mice were lower than those observed in infected WT mice, and CD4+ - and CD8+-producing IFN-γ cells were also reduced. These results strongly suggested that IFN-γ has a major role in the reduction of Treg cells. Thus we injected a neutralizing mAb against IFN-γ to infected Foxp3EGFP transgenic mice and unchanged Treg cell number was detected in blood. Our results thus demonstrate that exacerbated IFN-γ levels during acute toxoplasmosis are responsible of collapse of Treg cell number in this model.