Molecular analysis of pathogenicity congenital toxoplasmosis

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In order to establish a mouse experimental model of congenital toxoplasmosis by using INF-γ, TNF-α, and NKT KO pregnant mice were examined the infectivity of Toxoplasma gondii (T.gondii) (a cyst forming strain, Fukaya) to their fetuses. In IFN-g KO mouse model, 100% of placentas, 62% of fetal livers and 30% offetal brains of the new born babies from T.gondii-infected IFN-g KO pregnant mice were obtained. None of the babies of other strains were infected. Thus, an experimental congenital toxoplasmosis model has been established by using IFN-g KO mice. IFN-γ was shown to function as an abortion inducing factor to T.gondii-infected pregnant mice as well as anti-T.gondii function.One of the molecular mechanism of such bi-functional activity of IFN-γ was mediated by induction of NO synthesis from macrophages that caused tissue damage and anti-T.gondii activity. IFN-γ was shown to mediate anti-T.gondii activity in fetal livers and brains. Furthermore, IFN-γ induced the conversion of T.gondii from tachyzoites to bradyzoites at the placenta.We have cloned the full length HSP70 of Toxoplasma gondii (T.g.HSP70) which has been revealed to act as a virulent gene, or danger signal in T.gondii-infected mice. Using differential display method to analyze the genes controlling the susceptibility/resistance of mice to T.gondii infection, IFN-γ, TNF-α, IL-4, IL-5, STAT-1, STAT-2, IRF-1 genes were shown to be involved. Furthermore, more than 12 candidate genes are speculated to be involved in protective immunity to T.gondii infection. Fine analysis of these genes is underway.