Neutralization of maternal IL-4 modulates congenital protozoal transmission: Comparison of innate versus acquired immune responses

IL-4 levels were modulated in mice to test the hypothesis that induction of a maternal type 1 response would decrease the frequency of congenital Neos pora caninum transmission. This hypothesis tested the relationship between IL-4 and both innate and adaptive immunity utilizing two basic experimental designs. In the first, maternal IL-4 was neutralized with mAb during pregn ancy in naive mice concomitant with initial, virulent infection. In the sec ond, maternal IL-4 was neutralized before pregnancy concomitant with a prim ing inoculation consisting of live, avirulent N. caninum tachyzoites follow ed by virulent challenge during subsequent gestation. In mice that were nai ve before pregnancy, neutralization of IL-4 during gestational challenge di d not result in decreased congenital transmission as measured by PCR perfor med on 1-day-old neonatal mice. In mice that were primed and modulated befo re pregnancy, congenital transmission from gestational challenge was signif icantly decreased compared with control mice. Reduction in transmission con stituted a decrease in the numbers of mice transmitting N, caninum and a lo wer frequency of transmission by individual dams (p < 0.05). Decreased cong enital transmission was associated with significantly lower levels of mater nal splenocyte IL-4 secretion, lower IL-4 mRNA levels, and higher levels of IPN-gamma secretion. Protected mice had significantly decreased Neospora-s pecific IgG1 compared with nonmodulated mice. These studies define a-relati onship between maternal Ag-specific immunity and the frequency of congenita l transmission and demonstrate that modulation of type 2 cytokine responses can change the frequency of congenital protozoal transmission.