Maternal and foetal cytokine production in dams naturally and experimentally infected with Neospora caninum on gestation day 110

- IFN-γ, IL-17A and IL-4 production in pregnant dams experimentally infected with Neospora caninum and in their foetuses.
- Cytokine production compared in naturally infected and N. caninum experimentally infected dams, and in control pregnant dams.
- Protective immunity against abortion could not definitively linked to IFN-γ levels in cell culture supernatants.
- An important role was observed of an inverse IFN-γ/IL-4 balance in protecting against N. caninum abortion.

In the present study, IFN-γ (Th1), IL-17 A (Th17) and IL-4 (Th2) concentrations in response to concanavalin (ConA) and Neospora caninum antigen (Nc-1) stimulation were determined in cultures of cells from control uninfected (n = 4), naturally N. caninum-infected (n = 3) and experimentally N. caninum-infected (n = 6) pregnant dams and their foetuses. Experimental animals were infected at 110 days of gestation and euthanized 6 weeks post-infection. In culture supernatants from the dams, significantly higher IFN-γ and IL-4 levels were found in the experimentally-infected animals compared to the control or naturally-infected dams. However, among the experimentally-infected dams no significant differences in IFN-γ production were observed regardless of the incidence of live or aborted/dead foetuses, though spleen cultures of dams carrying live foetuses showed the highest levels of IFN-γ. IL-17A production was very low and occasional in the dams infected with N. caninum and did not seem to be a major regulator of IFN-γ production in this model. Experimentally infected dams with live foetuses showed higher IL-4 levels and accordingly IFN-γ/IL-4 ratios were significantly lower than ratios recorded for cows with aborted/dead foetuses. In the infected foetuses of these dams, only spleen cultures showed high levels of IFN-γ and IL-4 after Nc-1 antigen and ConA stimulation, respectively. No IL-17A was detected in the foetuses. As conclusion, although we could not clearly relate a protective immune response against N. caninum abortion only to IFN-γ levels in cell cultures, our results highlight the important role of an inverse IFN-γ/IL-4 balance in conferring protection against abortion induced by this parasite.