Susceptibility of human villous (BeWo) and extravillous (HTR-8/SVneo) trophoblast cells to Toxoplasma gondii infection is modulated by intracellular iron availability

The Availability of Iron Is Involved in the Murine Experimental Toxoplasma gondii Infection Outcome

“…The lower parasite load observed in the organ could be related to the iron deprivation for the parasite growth. Thus, as observed in vitro for the RH strain [22,46], the iron deprivation also is able to interfere in the ME-49 T. gondii strain growth in vivo. However, with our experimental protocol, the iron supplementation of animals with FeSO 4 was not able to increase the tissue parasitism in levels higher than those of infected untreated mice.…”

“…Many in vivo and in vitro studies have demonstrated that deferoxamine has beneficial effects in the treatment of protozoan infections, such as T. cruzi and P. berghei, being free of major hematological side effects [54][55][56]. As intestinal rat [20], human foreskin fibroblast (HFF) [46], and human trophoblast [22] cells treated with deferoxamine prevented T. gondii replication in a dose-dependent manner, we treated C57BL/6 mice by the oral route with deferoxamine and observed the infection outcome, mainly the parasite growth and lesions in the small intestine, lung, and liver in acute phase of infection. In the present investigation, it was observed that deferoxamine inhibited the growth of T. gondii in the small intestine.…”

“…In rat enterocytes or in peritoneal macrophages, Toxoplasma gondii and Trypanosoma cruzi replication, respectively, are iron-dependent [19,20]; and it was demonstrated that two T. gondii membrane rhoptry proteins (ROP4 and ROP2) bind to human lactoferrin, which could be involved in parasite pathogenic mechanisms such as invasion and replication in the parasitophorous vacuole [21]. Our group showed that the addition of holo-transferrin increased, and deferoxamine (DFO) treatment decreased the T. gondii multiplication in human villous (BeWo) and in extravillous (HTR-8/SVneo) trophoblast cells, as well as in human chorionic villous explants [22]. Regarding another apicomplexan parasite, it was shown that iron chelators led to a dose-dependent inhibition of Plasmodium exoerythrocytic forms development in vitro and decreased liver infection in mice [23].…”

Heme Oxygenase-1 Induction in Human BeWo Trophoblast Cells Decreases Toxoplasma gondii Proliferation in Association With the Upregulation of p38 MAPK Phosphorylation and IL-6 Production

“…The BeWo human choriocarcinoma cell line was obtained from American Type Culture Collection (CCL-98 TM , ATCC R , Manassas, VA, United States), and the HTR-8/SVneo human immortalized extravillous trophoblast cell line was kindly provided by Dr. Estela Bevilacqua (University of São Paulo, SP, Brazil). Both cell lines were cultured in 25 or 75 cm 2 culture flasks, in Roswell Park Memorial Institute (RPMI)-1640 medium (Cultilab, Campinas, SP, Brazil) supplemented with 2 mM L-glutamine, 100 U/ml penicillin, 100 µg/ml streptomycin (Sigma-Aldrich, St. Louis, MO, United States), and 10% heatinactivated fetal bovine serum (FBS) (Cultilab) (complete medium), in humidified incubator at 37 • C and 5% CO 2 (Almeida et al, 2019). According to protocol number 13/2012, the Ethics Committee of the Federal University of Uberlândia, MG, Brazil, determines that the commercially acquired cell lines do not require ethical approval.…”

“…HTR-8/SVneo extravillous trophoblast cells are non-tumorigenic and nonmetastatic cell line, synthesize human chorionic gonadotropin (hCG), and express markers of epithelial-mesenchymal transition (EMT) (Graham et al, 1993;Msheik et al, 2020). Specifically, in the present study, BeWo and HTR-8/SVneo cells were used, as several studies have been done related to the interaction of these cell phenotypes with T. gondii (Oliveira et al, 2006;Castro et al, 2013;Barbosa et al, 2014Barbosa et al, , 2015Guirelli et al, 2015;Almeida et al, 2019;Milian et al, 2019). Thus, these cell lines are promising models to investigate pathophysiology of T. gondii infection in trophoblast (Barbosa et al, 2015;Guirelli et al, 2015;Almeida et al, 2019).…”