B F Barbosa1, L Paulesu2, F Ietta3, N Bechi4, R Romagnoli5, A O Gomes6, S Favoreto-Junior7, D A O Silva8, J R Mineo9, T W P Mineo10, E A V Ferro11. 1. Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: bellisafb@icbim.ufu.br. 2. Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: luana.riccipaulesu@unisi.it. 3. Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: ietta@unisi.it. 4. Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: nikoniko29@libero.it. 5. Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: romagnolir@unisi.it. 6. Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: angellicagomes@yahoo.com.br. 7. Department of Biology, Cuesta College, Highway Road 1, San Luis Obispo, CA, United States. Electronic address: favoretojr@gmail.com. 8. Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: daosilva@yahoo.com.br. 9. Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: jrmineo@ufu.br. 10. Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: tiagomineo@gmail.com. 11. Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: eloisa@umuarama.ufu.br.
Abstract
INTRODUCTION: Macrophage migration inhibitory factor (MIF) participates in the immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E2 (PGE2) activation, but there is limited information on these mechanisms in human trophoblast. The present study aimed to verify the role of MIF in the ERK1/2 phosphorylation and PGE2 production, as well as its effect on the susceptibility to T. gondii in BeWo cells. METHODS: BeWo cells were treated with increasing concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE2 production by Western blotting and ELISA, respectively. Cells were also treated with increasing concentrations of rMIF, rPGE2, or ERK1/2 inhibitor and tested for T. gondii proliferation. The supernatants of cells treated with rPGE2 were assayed for cytokine production by ELISA or CBA. RESULTS: ERK1/2 phosphorylation and PGE2 production increased when the cells were treated with low MIF concentrations while the parasitism control occurred only at high MIF concentrations. STAg was unable to change ERK1/2 phosphorylation or PGE2 release. BeWo cells demonstrated increased T. gondii proliferation and reduced production of pro-inflammatory cytokines when treated with PGE2, while PD98059 diminished the parasite proliferation. DISCUSSION: The intracellular mechanisms triggered by MIF are dose-dependent in BeWo cells, and PGE2 is an important factor for the persistence of T. gondii at the maternal fetal interface. CONCLUSION: MIF was unable to control T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE2 expression were activated, demonstrating a critical effect of these mediators favoring parasite proliferation.
INTRODUCTION:Macrophage migration inhibitory factor (MIF) participates in the immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E2 (PGE2) activation, but there is limited information on these mechanisms in human trophoblast. The present study aimed to verify the role of MIF in the ERK1/2 phosphorylation and PGE2 production, as well as its effect on the susceptibility to T. gondii in BeWo cells. METHODS: BeWo cells were treated with increasing concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE2 production by Western blotting and ELISA, respectively. Cells were also treated with increasing concentrations of rMIF, rPGE2, or ERK1/2 inhibitor and tested for T. gondii proliferation. The supernatants of cells treated with rPGE2 were assayed for cytokine production by ELISA or CBA. RESULTS:ERK1/2 phosphorylation and PGE2 production increased when the cells were treated with low MIF concentrations while the parasitism control occurred only at high MIF concentrations. STAg was unable to change ERK1/2 phosphorylation or PGE2 release. BeWo cells demonstrated increased T. gondii proliferation and reduced production of pro-inflammatory cytokines when treated with PGE2, while PD98059 diminished the parasite proliferation. DISCUSSION: The intracellular mechanisms triggered by MIF are dose-dependent in BeWo cells, and PGE2 is an important factor for the persistence of T. gondii at the maternal fetal interface. CONCLUSION:MIF was unable to control T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE2 expression were activated, demonstrating a critical effect of these mediators favoring parasite proliferation.
Authors: Rafaela J da Silva; Angelica O Gomes; Priscila S Franco; Ariane S Pereira; Iliana C B Milian; Mayara Ribeiro; Paolo Fiorenzani; Maria C Dos Santos; José R Mineo; Neide M da Silva; Eloisa A V Ferro; Bellisa de Freitas Barbosa Journal: Front Cell Infect Microbiol Date: 2017-07-26 Impact factor: 5.293
Authors: Francesca Ietta; Emanuela Maioli; Elena Daveri; Juliana Gonzaga Oliveira; Rafaela José da Silva; Roberta Romagnoli; Laura Cresti; Anna Maria Avanzati; Luana Paulesu; Bellisa de Freitas Barbosa; Angelica de Oliveira Gomes; José Roberto Mineo; Eloisa Amália Vieira Ferro Journal: Sci Rep Date: 2017-04-28 Impact factor: 4.379
Authors: Fernando Gómez-Chávez; Irma Cañedo-Solares; Luz Belinda Ortiz-Alegría; Yevel Flores-García; Ricardo Figueroa-Damián; Héctor Luna-Pastén; Valeria Gómez-Toscano; Carlos López-Candiani; G Emmanuel Arce-Estrada; Christian A Bonilla-Ríos; Juan Carlos Mora-González; Ricardo García-Ruiz; Dolores Correa Journal: Front Immunol Date: 2020-03-13 Impact factor: 7.561