IFN-gamma overproduction and high level apoptosis are associated with highbut not low virulence Toxoplasma gondii infection

Toxoplasma gondii is an opportunistic intracellular parasite which induces a highly strong type 1 cytokine response. The present study focuses on defi ning the factors influencing the outcome of infection with tachyzoites of t he type 1, highly lethal RH strain, relative to the type II, low virulence strain ME49. Infection with the RH strain led to widespread parasite dissem ination and rapid death of mice; in contrast, mice survived low virulence s train ME49 infection, and tachyzoite dissemination was much less extensive. Furthermore, massive apoptosis and disintegration of the splenic architect ure was characteristic of RR, but not ME49, infection. In addition, hyperin duction of IFN-gamma and lack of NO production were found during RH, in con trast to ME49 infection. These data demonstrate that Toxoplasma strain char acteristics exert a profound effect on the host immune response and that th e latter itself is a crucial determinant in parasite virulence.