Immunopathogenesis of bovine neosporosis throughout gestation

Abstract

Despite Neospora caninum being recognised as a major cause of bovine abortion, its pathogenesis is only partially understood. Evidence of immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to an exacerbated Th1 immune 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 following infection in mid or late gestation. The aim of the current study was to characterise the placental cellular immune responses and cytokine expression following experimental Neospora infection during pregnancy. Placentomes were collected from cattle experimentally inoculated with the tachyzoites of the Nc-1 strain during early, mid and late gestation. Inflammation in early gestation was generally moderate to severe. Differently in mid gestation, inflammation was mild to moderate and minimal to mild in late gestation. Generally cellular infiltrates were mainly characterised by the presence of CD3+, CD4+ and γδ T-cells; whereas CD8+ and NK cells were less numerous. Macrophages were detected in larger numbers during later time-points after infection. A moderate to severe infiltration of IL-12, IFN-γ and TNF-α expressing cells was observed in the placentas collected in early gestation. This infiltration was more pronounced in the samples of placentome collected from dams carrying a dead foetus or in those that had aborted, compared with mothers carrying live foetuses at the time of sampling. The distribution of the cellular subsets observed in the three studies was similar. However, cellular infiltrates were more severe following infection during the first trimester in comparison to the second and third trimester. Similarly, the infiltration of Th1 cytokine expressing-cells was more severe in early gestation compared with the milder and more minimal infiltrations observed following N. caninum infection in mid and late gestation, respectively. These results may explain the milder clinical outcome observed when animals are infected in later stages of pregnancy.