Interferon gamma is involved in apoptosis of trophoblast cells at the maternal-fetal interface following Toxoplasma gondii infection

Abstract

Objective: To assess whether interferon gamma (IFN-γ) secreted by decidual natural killer (dNK) cells at the maternal-fetal interface is involved in the apoptosis of trophoblast cells (trophoblasts) following Toxoplasma gondii infection.

Methods: Human dNK cells were infected with T. gondii and then co-cultured with trophoblasts. The infected co-cultured cells were treated with or without IFN-γ neutralizing antibodies. Uninfected co-cultured cells were used as controls. The level of IFN-γ in the supernatant of co-culture was measured by ELISA and the apoptosis of trophoblasts was analyzed by flow cytometry. The expression of caspase 3 and caspase 8 of trophoblasts cells was determined by Western blotting and real-time RT-PCR.

Results: The levels of IFN-γ were increased at <24h following T. gondii infection and were maintained thereafter. Caspase 3, caspase 8, and the apoptosis of trophoblasts co-cultured with dNK cells were increased compared with the control. Meanwhile, IFN-γ, caspase 3, caspase 8, and trophoblast apoptosis were up-regulated upon increased ratios of dNK cells to trophoblasts. Compared to the infected group, the levels of IFN-γ, caspase 3, caspase 8, and trophoblast apoptosis were significantly decreased upon treatment with the IFN-γ neutralizing antibody. IFN-γ levels were correlated positively with the apoptosis of trophoblasts (r=0.7163, p < 0.01).

Conclusions: The levels of IFN-γ secreted by dNK cells at the maternal-fetal interface were closely correlated with the apoptosis of trophoblasts upon T. gondii infection. The apoptosis of trophoblasts induced by the increase in IFN-γ depended on the caspase pathway, which may contribute to the abnormal pregnancy outcomes that occur with T. gondii infection.

Keywords: Abnormal pregnancy outcomes; Apoptosis; IFN-γ; Toxoplasma gondii; Trophoblasts.