Maternal immune stimulation improves gestational outcome of congenital toxoplasmosis

Abstract

Toxoplasma gondii, a protozoan parasite annually infecting 1.5 million people in the US, can cause devastating effects if infection occurs during pregnancy. Congenital toxoplasmosis results in stillbirths, hydrocephalus, blindness, mental retardation, and neurological and behavioral disorders. In mice, maternal immune stimulation dramatically reduces teratogen induced birth defects. The protective effects of maternal immune stimulation on infectious causes of birth defects like congenital toxoplasmosis are unknown and were investigated. Mice were immune stimulated with IFNγ prior to breeding and were then infected orally with 30 T. gondii tissue cysts on day 3 of gestation. Fetal malformations and mortality was determined on gestational day 17 from the following treatment groups: Control, T. gondii only, IFNγ only, and IFNγ + T. gondii. Immune stimulation with IFNγ increased fetal survival from 23% to 58% and decreased fetal resorptions from 77% to 29% in T. gondii exposed fetuses. Proportionally more of the resorbed fetuses from IFNγ + T. gondii dams were late gestational indicating improved early embryonic survival. Unexpectedly, dams treated with IFNγ + T. gondii had a 30% mortality rate. Further studies are needed to identify the cause of maternal mortality and determine whether improved gestational outcome translates into improved postnatal function. Supported by USDA AD‐421 137196.