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.