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

Objective: To assess whether interferon gamma (IFN-gamma) 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-gamma neutralizing antibodies. Uninfected co-cultured cells were used as controls. The level of IFN-gamma 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-gamma were increased at <24 h 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-gamma, 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-gamma, caspase 3, caspase 8, and trophoblast apoptosis were significantly decreased upon treatment with the IFN-gamma neutralizing antibody. IFN-gamma levels were correlated positively with the apoptosis of trophoblasts (r = 0.7163, p < 0.01). Conclusions: The levels of IFN-gamma 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-gamma depended on the caspase pathway, which may contribute to the abnormal pregnancy outcomes that occur with T. gondii infection. (C) 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license.