Transforming growth factor (TGF)-β1 and interferon (IFN)-γ differentially regulate ICAM-1 expression and adhesion of Toxoplasma gondii to human trophoblast (BeWo) and uterine cervical (HeLa) cells

Teixeira, Samuel Cota; Silva, Rafaela J.; Lopes-Maria, Janice Buiate; Gomes, A. da S.; Angeloni, Mariana Bodini; Fermino, Marise Lopes; Roque‐Barreira, Maria Cristina; Silva, Neide M.; Silva, Deise A. O.; Mineo, José Roberto; Ferro, Eloísa Amália Vieira; Barbosa, Bellisa Freitas

doi:10.1016/j.actatropica.2021.106111

Cited by 8 publications

(4 citation statements)

References 82 publications

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“…Infections in BeWo showed that these cells are more susceptible to T. gondii than HeLa cells (uterine cervical tumor derived). Consistently, both cell lines produce different immune effectors in response to infection ( Pfaff et al., 2005b ; Oliveira et al., 2006 ).Additionally, ICAM-1 expression in both cell lines is differentially induced by TGF-β1 and IFN-γ, suggesting a different modulation of susceptibility to infection( Teixeira et al., 2021 ). Another interesting finding is the parasite’s ability to modulate apoptosis as an evasion strategy to survive.…”

Section: Cell Derived Models To Study T Gondii In ...mentioning

confidence: 89%

Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission

Faral-Tello

Pagotto

Bollati-Fogolín

et al. 2023

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of the most devastating consequences of toxoplasmosis. T. gondii can severely impact the pregnancy’s outcome causing miscarriages, stillbirths, premature births, babies with hydrocephalus, microcephaly or intellectual disability, and other later onset neurological, ophthalmological or auditory diseases. To tackle T. gondii’s vertical transmission, it is important to understand the mechanisms underlying host-parasite interactions at the maternal-fetal interface. Nonetheless, the complexity of the human placenta and the ethical concerns associated with its study, have narrowed the modeling of parasite vertical transmission to animal models, encompassing several unavoidable experimental limitations. Some of these difficulties have been overcome by the development of different human cell lines and a variety of primary cultures obtained from human placentas. These cellular models, though extremely valuable, have limited ability to recreate what happens in vivo. During the last decades, the development of new biomaterials and the increase in stem cell knowledge have led to the generation of more physiologically relevant in vitro models. These cell cultures incorporate new dimensions and cellular diversity, emerging as promising tools for unraveling the poorly understood T. gondii´s infection mechanisms during pregnancy. Herein, we review the state of the art of 2D and 3D cultures to approach the biology of T. gondii pertaining to vertical transmission, highlighting the challenges and experimental opportunities of these up-and-coming experimental platforms.

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Section: Cell Derived Models To Study T Gondii In ...mentioning

confidence: 89%

Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission

Faral-Tello

Pagotto

Bollati-Fogolín

et al. 2023

Front. Cell. Infect. Microbiol.

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“…In order to assess the impact of both the leaf hydroalcoholic extract and oleoresin from C. multijuga in the T. gondii infection, we used BeWo and HTR8/SVneo cells as villous and extravillous trophoblast cell models, respectively, being considered as excellent experimental models for the study of congenital toxoplasmosis in vitro ( Barbosa et al., 2014 ; Souza et al., 2021 ; Teixeira et al., 2021 ). Firstly, the viability assay was performed.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, finding active and less toxic drugs as new therapeutic strategies to prevent or treat congenital toxoplasmosis is absolutely necessary and encouraging. Our previous studies have shown alternative drugs or potential molecular targets with great effects against T. gondii infection ( Costa et al., 2009 ; Souza et al., 2021 ; Teixeira et al., 2021 ). Thus, it is important to highlight the importance of studying alternative treatments for the control of T. gondii infection.…”

Section: Introductionmentioning

confidence: 99%

“…As experimental models, we used BeWo and HTR8/SVneo cells, representatives of human villous and extravillous trophoblasts, respectively, as well as human villous explants as an experimental model of maternal-fetal interface. Our research group widely uses these cells and explants in studies about human maternal-fetal interface ( Barbosa et al., 2014 ; Barbosa et al., 2015 ; Teixeira et al., 2020 ; Souza et al., 2021 ; Teixeira et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Martínez

Teixeira²,

Souza³

et al. 2023

Front. Cell. Infect. Microbiol.

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The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

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Effect of Maternal Body Mass Index on the Transcriptomic Network of Human First-Trimester Chorionic Villi

Dong

Pang

et al. 2022

Reprod. Sci.

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Transforming growth factor (TGF)-β1 and interferon (IFN)-γ differentially regulate ICAM-1 expression and adhesion of Toxoplasma gondii to human trophoblast (BeWo) and uterine cervical (HeLa) cells

Cited by 8 publications

References 82 publications

Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission

Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Effect of Maternal Body Mass Index on the Transcriptomic Network of Human First-Trimester Chorionic Villi

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