Characterization of the immune cell response in the placentas from cattle following experimental inoculation with Neospora caninum throughout pregnancy

Abstract

Despite Neospora caninum (NC) being a major cause of bovine abortion worldwide, its pathogenesis is not completely understood. Evidence of immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to the adverse effect of an exacerbated Th1 response at the maternal-foetal interface. Different clinical outcomes are known to follow experimental infections at different stages of gestation, with foetal death being the most common finding during early gestation infections, and the birth of live congenitally infected calves upon infection at mid or late gestation. The aim of our studies was to characterise placental immune responses following experimental infection during pregnancy. Cows were infected with NC tachyzoites at day 70, 140 and 210 of pregnancy and culled at 14, 28, 42 and 56 days post inoculation. Placentomes were examined by immunohistochemistry using antibodies against macrophages, T-cells (CD3, CD4, CD8, ¿¿TCR), NK and B cells and by in situ hybridization to characterize cytokine expression (IL-12, IFN-¿, TNF-¿ and IL-4). Inflammation was mainly characterised by the presence of CD3+, CD4+ and ¿¿ T-cells during the three time points. In early gestation inflammation was generally moderate to severe and mainly characterized by infiltration of IL-12, IFN-¿ and TNF-¿ expressing cells. This infiltration was more pronounced in the samples of placentome collected from dams carrying a dead foetus or one that had aborted, compared with the mothers carrying live foetuses at the time of sampling. In contrast, the infiltration of CD3+, CD4+, CD8+ and ¿¿ T-cells and Th1 cytokine expressing-cells was less evident following NC infection at mid gestation and scarce during infection at late gestation. These findings may partially explain the milder clinical outcome observed when animals are infected with NC at mid or late gestation.