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 (STAT)-1, 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 since 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.

Barbosa, B.F., Lopes Maria, J.B., Gomes, A.O., Angeloni, M.B., Castro, A.S., Franco, P.S., et al. (2015). IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells. BIOLOGY OF REPRODUCTION, 92(3), 1-13 [10.1095/biolreprod.114.124115].

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells

IETTA, FRANCESCA;
2015

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 (STAT)-1, 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 since 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.
Barbosa, B.F., Lopes Maria, J.B., Gomes, A.O., Angeloni, M.B., Castro, A.S., Franco, P.S., et al. (2015). IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells. BIOLOGY OF REPRODUCTION, 92(3), 1-13 [10.1095/biolreprod.114.124115].
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Descrizione: This is a pre-copyedited, author-produced version of an article accepted for publication in BIOLOGY OF REPRODUCTION following peer review. The version of record BIOLOGY OF REPRODUCTION (2015) 92(3):82, 1–13 Published online before print 11 February 2015 is available online at: 10.1095/biolreprod.114.124115
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/974831