Cytokine gene expression in aborting and non-aborting dams and in their foetuses after experimental infection with Neospora caninum at 110 days of gestation

Neospora caninum is a major cause of abortion in cattle. However, it is not known why not all infected animals abort. In this study, Th1 (IFN-gamma), Th2 (IL4) and T reg (IL-10) cytokine gene expression was examined by real time PCR using the TaqMan approach in all of these dams and their foetuses after experimental infection with the isolate Nc-Spain7 at 110 days of pregnancy and euthanasia 6 weeks after infection. In prior published work, foetal death was observed in three of six infected dams and transplacental infection in all the 6 infected foetuses. In the spleen of the dams, IL-4 expression was down-regulated in dams with aborted/non viable foetuses compared to both uninfected dams (controls, n = 3) and infected dams with live fetuses at euthanasia. In the lymph nodes draining the placenta, up-regulated expression of IL-4 was observed in infected dams with live foetuses compared to control dams. In the placenta, infected dams with live foetuses had significantly up-regulated IFN-gamma in both caruncle and cotyledon and up-regulated IL-10 in cotyledon compared to control dams. Infected live foetuses showed up-regulated expression of IFN-gamma and IL-10 in foetal spleen, and showed downregulated expression of IL-4 in the thymus compared to control uninfected foetuses. Expression of any cytokine in the thymus was significantly lower compared to the levels observed in foetal spleen. The results indicate an up-regulated expression of Th1, Th2 and Treg in infected dams with live foetuses and in their foetuses. On the other hand, down-regulation of Th2 immune responses and Treg cytokines were observed in infected dams which had aborted or had non-viable foetuses at euthanasia, suggesting an immunological recovery of cytokine gene expression levels in dams a few weeks after an abortion occurred. The authors thank Ana Burton for assistance with the English translation. This study was supported by a grant from the Spanish MINECO (AGL2012-39830-C02-01/02) and FEDER. The authors would like to thank the farmers who provided the experimental animals.