Comparison of the maternal and foetal immune responses of cattle, following an experimental inoculation with Neospora caninum at early, mid and late gestation

Abstract

The following experiments describe the maternal and foetal immune responses in cattle following a subcutaneous inoculation with live Neospora caninum tachyzoites at 70, 140 and 210 days of gestation (dg). At each stage of pregnancy a serial analysis of the maternal and foetal local and peripheral immune responses was conducted at 14, 28, 42 and 56 days post inoculation (dpi). At 70dg, foetal deaths were recorded from 28dpi onwards, challenged dams carrying live foetuses showed consistently higher levels of cellular proliferation and significantly (p≤0.05) higher levels of IFN-γ compared to those carrying dead foetuses. Samples of foetal spleen, thymus and PBMC demonstrated cellular proliferation as well as IFN-γ, IL-4, IL-10 and IL-12 production following mitogenic stimulation with Con A from 14dpi (day 84 gestation) onwards. At 140dg, PBMC from all challenged dams demonstrated antigen specific proliferation and IFN-γ production by 7dpi. Challenged dams seroconverted producing Neospora-specific IgG from 7-14dpi, while anti-Neospora antibodies were detected in the foetuses from 42dpi. Maternal and foetal Neospora-specific CMI responses were demonstrated in local and peripheral lymph nodes by 14dpi and 28dpi respectively. On 42dpi phenotypic analysis of the responding cells showed that they were predominantly CD4+ T-cells, in both dams and foetuses. At 210dg, seroconvertion of the dams occurred between 7-14dpi, while significantly (p≤0.05) increased levels of cellular proliferation and production of IFN-γ were seen in both the maternal and foetal local and peripheral lymph nodes of the challenged animals from 14dpi, along with increased levels of IL-4 and IL-10. From 28dpi significant (p≤0.05) increases in expression of TLR-2 and TLR-9 were observed in challenged dams, while increased levels of both TLR-2 and TLR-9 were seen in the foetuses of challenged dams. Our results show that robust maternal and foetal immune responses are required to ensure foetal survival following a challenge with N. caninum.