Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Abstract Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, a...

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Autores principales: Guilherme de Souza, Rafaela José Silva, Iliana Claudia Balga Milián, Alessandra Monteiro Rosini, Thádia Evelyn de Araújo, Samuel Cota Teixeira, Mário Cézar Oliveira, Priscila Silva Franco, Claudio Vieira da Silva, José Roberto Mineo, Neide Maria Silva, Eloisa Amália Vieira Ferro, Bellisa Freitas Barbosa
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/82b945ba401f4713b702502e03124623
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spelling oai:doaj.org-article:82b945ba401f4713b702502e031246232021-12-02T17:41:09ZCyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants10.1038/s41598-021-92120-32045-2322https://doaj.org/article/82b945ba401f4713b702502e031246232021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92120-3https://doaj.org/toc/2045-2322Abstract Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-β1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.Guilherme de SouzaRafaela José SilvaIliana Claudia Balga MiliánAlessandra Monteiro RosiniThádia Evelyn de AraújoSamuel Cota TeixeiraMário Cézar OliveiraPriscila Silva FrancoClaudio Vieira da SilvaJosé Roberto MineoNeide Maria SilvaEloisa Amália Vieira FerroBellisa Freitas BarbosaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Guilherme de Souza
Rafaela José Silva
Iliana Claudia Balga Milián
Alessandra Monteiro Rosini
Thádia Evelyn de Araújo
Samuel Cota Teixeira
Mário Cézar Oliveira
Priscila Silva Franco
Claudio Vieira da Silva
José Roberto Mineo
Neide Maria Silva
Eloisa Amália Vieira Ferro
Bellisa Freitas Barbosa
Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
description Abstract Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-β1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.
format article
author Guilherme de Souza
Rafaela José Silva
Iliana Claudia Balga Milián
Alessandra Monteiro Rosini
Thádia Evelyn de Araújo
Samuel Cota Teixeira
Mário Cézar Oliveira
Priscila Silva Franco
Claudio Vieira da Silva
José Roberto Mineo
Neide Maria Silva
Eloisa Amália Vieira Ferro
Bellisa Freitas Barbosa
author_facet Guilherme de Souza
Rafaela José Silva
Iliana Claudia Balga Milián
Alessandra Monteiro Rosini
Thádia Evelyn de Araújo
Samuel Cota Teixeira
Mário Cézar Oliveira
Priscila Silva Franco
Claudio Vieira da Silva
José Roberto Mineo
Neide Maria Silva
Eloisa Amália Vieira Ferro
Bellisa Freitas Barbosa
author_sort Guilherme de Souza
title Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
title_short Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
title_full Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
title_fullStr Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
title_full_unstemmed Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
title_sort cyclooxygenase (cox)-2 modulates toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/82b945ba401f4713b702502e03124623
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