P M Guirelli1, M B Angeloni2, B F Barbosa3, A O Gomes4, A S Castro5, P S Franco6, R J Silva7, J G Oliveira8, O A Martins-Filho9, J R Mineo10, F Ietta11, E A Ferro12. 1. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: pamelaguirelli@gmail.com. 2. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: ma_bodini@yahoo.com.br. 3. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: bellisafb@icbim.ufu.br. 4. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: angellicagomes@yahoo.com.br. 5. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: ascastro87@yahoo.com.br. 6. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: pribio85@hotmail.com. 7. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: rafaela_jsilva@hotmail.com. 8. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: julianago@icbim.ufu.br. 9. Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, Oswaldo Cruz Foundation, 30190-002 Belo Horizonte, MG, Brazil. Electronic address: oamfilho@cpqrr.fiocurz.br. 10. Laboratory of Immunoparasitology, Department of Immunology, Microbiology and Parasitology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: jrmineo@ufu.br. 11. Department of Life Science, University of Siena, Via Aldo Moro 2, Siena, Italy. Electronic address: ietta@unisi.it. 12. Laboratory of Immunophysiology of Reproduction, Department of Histology and Embryology, Federal University of Uberlândia, Av. Pará, 1720, Uberlândia, CEP 38400 902, Brazil. Electronic address: eloisa@umuarama.ufu.br.
Abstract
INTRODUCTION: The interaction between human extravillous trophoblasts and macrophages has an important role in implantation and placentation. However, any dysfunction in this communication system is associated with pregnancy pitfalls, and a Toxoplasma gondii infection can be a potential problem in this crosstalk. Therefore, the aim of this study was to assess the influence of infected macrophages on cytokine production and the incidence of apoptosis in T. gondii-infected extravillous trophoblast cells. METHODS: HTR-8/SVneo cells were treated with supernatant from macrophages infected or not by T. gondii (conditioned medium) in order to analyze apoptosis and cytokine production in comparison to uninfected control conditions. RESULTS: The IL-6 secretion by HTR-8/SVneo cells increased synergistically by treatment with conditioned medium and T. gondii infection. The apoptosis index of HTR-8/SVneo cells was also upregulated by treatment with conditioned medium and infection. In addition, a low expression of Fas/CD95 and a high soluble FasL release were observed during infection, although no significant change was observed in the proliferation of T. gondii. DISCUSSION: The parasite modulates the high apoptosis index in HTR-8/SVneo cells in order to favor its establishment inside its host cells. On the other hand, the conditioned medium from uninfected macrophages restores the apoptosis rates, although the effect of the infection seems to be stronger. In conclusion, our results showed that T. gondii infection in human extravillous trophoblasts is able to modulate the trophoblast-macrophage crosstalk.
INTRODUCTION: The interaction between human extravillous trophoblasts and macrophages has an important role in implantation and placentation. However, any dysfunction in this communication system is associated with pregnancy pitfalls, and a Toxoplasma gondii infection can be a potential problem in this crosstalk. Therefore, the aim of this study was to assess the influence of infected macrophages on cytokine production and the incidence of apoptosis in T. gondii-infected extravillous trophoblast cells. METHODS: HTR-8/SVneo cells were treated with supernatant from macrophages infected or not by T. gondii (conditioned medium) in order to analyze apoptosis and cytokine production in comparison to uninfected control conditions. RESULTS: The IL-6 secretion by HTR-8/SVneo cells increased synergistically by treatment with conditioned medium and T. gondii infection. The apoptosis index of HTR-8/SVneo cells was also upregulated by treatment with conditioned medium and infection. In addition, a low expression of Fas/CD95 and a high soluble FasL release were observed during infection, although no significant change was observed in the proliferation of T. gondii. DISCUSSION: The parasite modulates the high apoptosis index in HTR-8/SVneo cells in order to favor its establishment inside its host cells. On the other hand, the conditioned medium from uninfected macrophages restores the apoptosis rates, although the effect of the infection seems to be stronger. In conclusion, our results showed that T. gondii infection in human extravillous trophoblasts is able to modulate the trophoblast-macrophage crosstalk.