title: IL10, TGF beta1, and IFN gamma modulate intracellular signaling pathways and cytokine production to control Toxoplasma gondii infection in BeWo trophoblast cells.
abstract: Considering that interleukin 10 (IL10), transforming growth factor beta1 (TGFB1), and interferon gamma (IFNG) are involved in the susceptibility of BeWo trophoblast cells to Toxoplasma gondii infection, the aim of the present study was to investigate the effector mechanisms triggered by these cytokines in the control of T. gondii in BeWo cells. For this purpose, infected/uninfected BeWo cells were treated with IL10, TGFB1 (50 ng/ml), and IFNG (20 or 100 ng/ml) in order to verify the phosphorylation of signal transducers and activators of transcription 1 (STAT1), STAT3, and Smad2, parasite intracellular proliferation, as well as the Th1/Th2/IL17A cytokine production. The treatment of BeWo cells with IL10 and TGFB1 favored T. gondii proliferation, and these findings were associated with STAT3 and Smad2 phosphorylation, respectively (P < 0.05). Also, these cytokine treatments were able to down-modulate TNF alpha (TNFA) and IL6 production (P < 0.05). Low concentration of IFNG was unable to control T. gondii infection but was able to trigger STAT1 phosphorylation and up-regulate IL6 and IL17A production; whereas a high concentration of IFNG was unable to activate STAT1 but down-modulated IL6 and TNFA and increased T. gondii proliferation (P < 0.05). IL10, TGFB1, and IFNG regulate a differential T. gondii proliferation in BeWo cells because they distinctly trigger intracellular signaling pathways and cytokine production, especially IL6 and TNFA. Our data open new windows to understand the mechanisms triggered by IL10, TGFB1, and IFNG at the maternal-fetal interface in the presence of T. gondii, contributing to recognizing the importance of these effector mechanisms involved in the vertical transmission of this parasite.
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Bellisa Freitas
authors: BF
authors: Barbosa
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Janice Buiate
authors: JB
authors: Lopes-Maria
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Angelica Oliveira
authors: AO
authors: Gomes
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Mariana Bodini
authors: MB
authors: Angeloni
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Andressa Silva
authors: AS
authors: Castro
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Priscila Silva
authors: PS
authors: Franco
authors: Department of Cellular and Molecular Biology, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Marise Lopes
authors: ML
authors: Fermino
authors: Department of Cellular and Molecular Biology, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Maria Cristina
authors: MC
authors: Roque-Barreira
authors: Department of Life Science, University of Siena, Siena, Italy.
authors: Francesca
authors: F
authors: Ietta
authors: Laboratory of Chagas Disease, René Rachou Research Center, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors: Olindo Assis
authors: OA
authors: Martins-Filho
authors: Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: Deise Aparecida Oliveira
authors: DA
authors: Silva
authors: Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors: José Roberto
authors: JR
authors: Mineo
authors: Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil eloisa@umuarama.ufu.br.
authors: Eloisa Amália Vieira
authors: EA
authors: Ferro
mesh_terms: D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D019410:Interleukin-16 / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism; D014122:Toxoplasma / Q000302:isolation & purification; D014123:Toxoplasmosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014594:Uterine Neoplasms / Q000473:pathology
chemical_list: D016207:Cytokines; D019410:Interleukin-16; C497782:SMAD2 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Toxoplasma gondii; cytokines; signaling pathways; trophoblast cells