Analysis of local and peripheral immune response developed in sheep experimentally infected with Toxoplasma gondii at different times of gestation

Abstract

Toxoplasmosis is one the main infectious causes of reproductive failure in sheep where the time of gestation when sheep are infected affects the clinical and lesional outcome of the disease. In order to investigate the variations of local and peripheral immune responses during gestation, pregnant sheep were infected at early, mid and late gestation and subsequently culled at 2, 3 and 4 weeks post infection. In those sheep inoculated during the second term, serological antibodies were detected earlier and the increase in serological γ-IFN was higher than in the other infected animals. Regarding the local immune response at the placenta, infiltration of inflammatory cells was mainly found in the maternal septa, although it also invaded foetal mesenchyme adjacent to the lesions. The increase in the number of T lymphocytes was observed only in ewes infected during the second and last terms of gestation while the increase of B cells occurred in sheep infected at the first and second terms. The expression of iba-1 antigen by macrophages was more frequent after infection during the first term whereas macrophages expressing lysozyme, CD163 or calprotectin were more frequent in infections at mid-gestation. A significant increase in the transcription of γ-IFN, when compared to control animals, occurred after infections in the first and second term, while TNF-α and IL-10 transcription increased only in the second and last term, respectively. There were no differences when comparing transcription of cytokines between animals infected at different terms of gestation. This study shows that the time of gestation when infection occurs has a clear influence over the pathogenesis of ovine toxoplasmosis as a greater inflammatory response was found after inoculating sheep at the second term of gestation. This finding may explain the later invasion of the placenta by the parasite at early and mid gestation described in previous studies.