Biogenic Silver Nanoparticles Can Control Toxoplasma gondii Infection in Both Human Trophoblast Cells and Villous Explants

Abstract

The combination of sulfadiazine and pyrimethamine plus folinic acid is the conventional treatment for congenital toxoplasmosis. However, this classical treatment presents teratogenic effects and bone marrow suppression. In this sense, new therapeutic strategies are necessary to reduce these effects and improve the control of infection. In this context, biogenic silver nanoparticles (AgNp-Bio) appear as a promising alternative since they have antimicrobial, antiviral, and antiparasitic activity. The purpose of this study to investigate the action of AgNp-Bio in BeWo cells, HTR-8/SVneo cells and villous explants and its effects against Toxoplasma gondii infection. Both cells and villous explants were treated with different concentrations of AgNp-Bio or combination of sulfadiazine + pyrimethamine (SDZ + PYZ) in order to verify the viability. After, cells and villi were infected and treated with AgNp-Bio or SDZ + PYZ in different concentrations to ascertain the parasite proliferation and cytokine production profile. AgNp-Bio treatment did not reduce the cell viability and villous explants. Significant reduction was observed in parasite replication in both cells and villous explants treated with silver nanoparticles and classical treatment. The AgNp-Bio treatment increased of IL-4 and IL-10 by BeWo cells, while HTR8/SVneo cells produced macrophage migration inhibitory factor (MIF) and IL-4. In the presence of T. gondii, the treatment induced high levels of MIF production by BeWo cells and IL-6 by HTR8SV/neo. In villous explants, the AgNp-Bio treatment downregulated production of IL-4, IL-6, and IL-8 after infection. In conclusion, AgNp-Bio can decrease T. gondii infection in trophoblast cells and villous explants. Therefore, this treatment demonstrated the ability to reduce the T. gondii proliferation with induction of inflammatory mediators in the cells and independent of mediators in chorionic villus which we consider the use of AgNp-Bio promising in the treatment of toxoplasmosis in BeWo and HTR8/SVneo cell models and in chorionic villi.

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

“…In this sense, combining our findings with literature, we hypothesized that the reduction in TNF-α levels, as result of COX-2 inhibition, may culminate in a decrease of PGE 2 production by infected villous, which could explain the impairment of the parasite growth. Taken together, in agreement with published studies, our data reveal a different cytokine profile between human trophoblast cells and villous explants from human third trimester pregnancy in the context of T. gondii 56 , 57 , 60 . In this context, we suggested that these differences among both models may be explained, in part, due to the fact that human villous is a tissue composed of mesenchyme, villous and extravillous trophoblast and syncytiotrophoblast, culminating in a distinct cytokine production.…”

“…Additionally, we also evaluated the functional role of COX-2 in the immune response and lipid droplets formation in these experimental models. Our research group has investigated the mechanisms of T. gondii infection in trophoblast cells using BeWo 54 – 57 and HTR-8/SVneo 58 – 60 cell lines as villous and extravillous trophoblast cells models, respectively, and human chorionic villous explants as maternal–fetal interface experimental model 56 , 60 – 62 .…”

Inhibition of Toxoplasma gondii Growth by Dihydroquinine and Its Mechanisms of Action

“…At 24 h, wells were washed with 1× phosphate-buffered saline (PBS) twice, and 100 µl of RH-RFP (6.3 × 10 4 cells/well) tachyzoites was added to the same 96-well plates and allowed to infect host cells for 3 h at 37°C with 5% CO 2 and 95% atmospheric air ( Leesombun et al., 2016 ; Zhang et al., 2019a ; Zhang et al., 2019b ; Salin et al., 2020 ; Contreras et al., 2021 ; Wang et al., 2021 ). At 3 h, plates were removed from the incubator, and extracellular parasites and the medium were washed off twice with 1× PBS followed by the addition of drugs serially diluted using procedures published by ( Salin et al., 2020 ; Nurkanto et al., 2021 ; Costa et al., 2021 ). A volume of 100 µl of DHQ (0, 3.13, 6.25, 12.5, 25, and 50 µM), positive controls (SZ and PY with concentrations of 0, 3.13, 6.25, 12.5, 25, and 50 µM), and negative control (culture media) were added to the designated wells.…”

Characterization and potential applications of silver nanoparticles: an insight on different mechanisms

“…In Hela cell line an increase in the NO concentration, oxidative stress and reduction of pro-inflammatory cytokines, in particular, IL-8 were observed. Thus, silver nanoparticles can significantly inhibit the spread of T. Gondi without developing dysfunction of the host cells (Figure 6b) [150,151]. In addition to the cell cultures and chorion-ic villi, AgNPs suppresses toxoplasma's replication in liver and spleen tissues [152].…”