title: 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.
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Binzhou Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, PR China.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Xianbing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Ou
authors.affiliation: Department of Immunology, Binzhou Medical University, No. 346 Guan-Hai Road, Lai-shan, Yantai, Shandong 264003, PR China; Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, PR China. Electronic address: xue-mei-hu@163.com.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
mesh_terms: D017209:Apoptosis; D018920:Coculture Techniques; D003656:Decidua / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D011247:Pregnancy; D014122:Toxoplasma; D014327:Trophoblasts / Q000276:immunology* / Q000469:parasitology*
chemical_list: D007371:Interferon-gamma
keywords: Abnormal pregnancy outcomes; Apoptosis; IFN-γ; Toxoplasma gondii; Trophoblasts