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

Guilherme De Souza,Samuel Cota Teixeira,Mário Cézar Oliveira,José Roberto Mineo,Thádia Evelyn De Araújo,Iliana Claudia Balga Milián,Claudio Vieira Da Silva,Alessandra Monteiro Rosini,Neide Maria Silva,Priscila Silva Franco,Eloisa Amália Vieira Ferro,Rafaela José Silva,Bellisa Freitas Barbosa

doi:10.1038/s41598-021-92120-3

Guilherme De Souza, Samuel Cota Teixeira + Show 11 more

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https://doi.org/10.1038/s41598-021-92120-3

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Journal: Scientific Reports	Publication Date: Jun 16, 2021
Citations: 24	License type: open-access

Affiliation: Universidade Federal de Uberlândia

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.

Highlights

Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus
We evaluated the cellular viability of BeWo and HTR-8/SVneo cells treated with COX-2 inhibitors, meloxicam or celecoxib, at different concentrations (Fig. 1)
When we evaluated the role of COX-2 in ex vivo model, we observed that human villous explants infected with T. gondii and treated with COX-2 inhibitors reduced T. gondii intracellular proliferation, upregulated migration inhibition fator (MIF) and downmodulated tumor necrosis factor (TNF) and IL-10 (Fig. 10B)

Summary

Introduction

Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. It is important to have a balance between a Th1 and Th2 profile This balance can be mediated by anti-inflammatory cytokines production, such as IL-4, IL-10 and transforming growth fator (TGF)-β1, which act by decreasing NO production in macrophages and cytotoxic activity of NK cells[17,18]. In pregnancy, this immune regulation mediated by anti-inflammatory and regulatory cytokines is important for the developmnet of the placenta and protection of the semiallogeneic fetus from maternal immune response[19,20]. It was shown that the ability to increase LDs production was conserved in three T. gondii strains (I—RH, II—ME-49; III- CEP)[40]

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