HATA Hidekazu Chiba University, School of Medicine, Assistant, 医学部, 助手 (00110304)
NOROSE Kazumi Chiba University, School of Medicine, Assistant, 医学部, 助手 (30156244)
AOSAI Fumie Chiba University, School of Medicine, Associate Professor, 医学部, 助教授 (80150316)
|Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
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.