Resistance to Toxoplasma gondii in mice infected as neonates or exposed in utero

Abstract

Mice were exposed to the protozoan parasite Toxoplasma gondii in utero or were infected as neonates in order to identify and characterize resistance mechanisms that function protectively during the first weeks after birth. About one-half of the mice born of mothers fed T. gondii cysts at 11 days of gestation survived to weaning age or beyond. No effect of major histocompatibility complex (MHC) haplotype on early survival was observed in a group of backcross progeny; however, long-term survival was strongly dependent on MHC haplotype. The ability of mice infected as neonates to survive until weaning was found to depend on gamma interferon and on Thy-1+ cells but not on CD4+ or CD8+ cells. Mice that survived to maturity after infection as neonates were slightly more resistant to challenge with virulent T. gondii parasites than were sham-infected controls but were less resistant than were mice infected as adults. Together the results indicate the following. (i) Mice congenitally infected with T. gondii have a gamma interferon-dependent mechanism of early resistance that involves Thy-1+ cells but not CD4+ or CD8+ cells. (ii) This mechanism is not under MHC-linked genetic control. (iii) Mice that exhibit long-term survival after congenital infection acquire a modest degree of protection against reinfection with virulent organisms. (iv) The extent of long-term survival of congenitally infected neonates, like that in mice infected as adults, is influenced by MHC genes, presumably via MHC-restricted CD4+ and/or CD8+ cells.