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.
Highlights
The intracellular protozoan Toxoplasma gondii is the etiologic agent of toxoplasmosis who affects about 30–50% of the world’s population (Montazeri et al, 2017)
No change in the viability was observed for HTR-8/SVneo cell treated with AgNp-Bio (Figure 1B)
We have demonstrated in our previous studies that IL-6 is an important cytokine involved in the control of T. gondii (Castro et al, 2013; Barbosa et al, 2015; da Silva et al, 2017; Almeida et al, 2019), while IL-8 seems to favor the parasite replication in trophoblast cells (Milian et al, 2019)
Summary
The intracellular protozoan Toxoplasma gondii is the etiologic agent of toxoplasmosis who affects about 30–50% of the world’s population (Montazeri et al, 2017) It is responsible for important clinical conditions in immunocompromised individuals (Atilla et al, 2015; Sutterland et al, 2015; Alday et al, 2017) and congenital toxoplasmosis, mainly in the first gestational months (Kodjikian, 2010). Macrophage migration inhibitory factor (MIF), produced by different cell types, is another cytokine with an important role in T. gondii infection (Bernhagen et al, 1998). This cytokine participates in dendritic cell maturation and acts in IL-1β, IL-12 and TNF production in the presence of T. gondii (Terrazas et al, 2010). Our previous studies demonstrated that BeWo cells and villous explants infected by T. gondii release MIF and IL-6 (Franco et al, 2011; Gomes et al, 2011; Castro et al, 2013; Barbosa et al, 2014, 2015; Abou-kheir et al, 2017; da Silva et al, 2017)
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