Dynamics of Cytokine Regulation of Immunopathology in Mice Infected with Type I RH and Type II ME49 Toxoplasma gondii Strains - Abstract
A variety of host and parasite factors determine the outcome of Toxoplasma gondii infection and mice are generally used as an animal model to study these outcomes. In the present study, we studied the immunopathogenic characteristics of type I RH and type II ME49 T. gondii parasites in MF1 mice by correlating the dynamics of the pro-inflammatory cytokines IFN-?, TNF-?, IL-18 and anti-inflammatory cytokines IL-4 and IL-10 in the blood and spleen tissue with the tissue pathology. All the mice died within 7 days post-infection with 100 tachyzoites of RH parasites however, the majority of mice inoculated orally with 10 cysts of ME49 developed a chronic infection and survived >84 days. Mice infected with RH parasites showed a strong Th2 response followed by a Th1 response characterized by extensive tissue damage. No IFN-? was detected in the blood during the early stages of infection by day 3 which then increased sharply on day 4 and remained high till day 7 when the mice died. All pro-inflammatory cytokines measured in the spleen tissue on day 3 post-RH infection showed an increase. In mice infected with type II ME49 T. gondii parasites, there was a significant increase in the pro-inflammatory cytokines in the spleen tissue during the early stages (day3-7) of infection however, in contrast to most earlier studies
using BALB/c and C57BL mice, no increase in TNF-? and IFN-? was observed in the blood during the 1st week which then showed a marked increase during the 2nd week of infection. The cytokine profile switched to an anti-inflammatory Th2 response during the intermediate stages (day 14-28) of the infection characterized by chronicity of infection with minimal tissue damage. During the late stages (day 42-84) of infection, a pro-inflammatory Th1 immune response was observed, associated with marked tissue damage.