Apoptosis and S Phase of the Cell Cycle in BeWo Trophoblastic and HeLa Cells are Differentially Modulated by Toxoplasma gondii Strain Types

Abstract

Transplacental transmission of Toxoplasma gondii causes congenital toxoplasmosis, one of the most severe forms of infection. The ability of the parasite to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of the host cells. During pregnancy, however, alterations in the incidence of apoptosis are associated with abnormal placental morphology and function. The aim of this study was to evaluate the incidence of apoptosis and cell proliferation in trophoblastic (BeWo cell line) and uterine cervical (HeLa cell line) cells infected with a highly virulent RH strain or a moderately virulent ME49 strain of T. gondii. BeWo and HeLa cells were infected with RH or ME49 tachyzoites (2:1 and 5:1; parasite:cell) or medium alone (control). After 2 h, 6 h and 12 h of incubation, cells were fixed in 10% formalin and analyzed by immunohistochemistry to determine the apoptosis (expression of cytokeratin 18 neo-epitope--clone M30) and cell in S phase (expression of proliferating cell nuclear antigen--PCNA) indices. RH strain-infected BeWo and HeLa cells showed a lower apoptosis index than non-infected controls, whereas a higher apoptosis index was found in ME49 strain-infected cells compared to controls. In addition, RH-infected cells displayed lower apoptosis index than ME49-infected cells, even though active caspase-3 was detected in both cell types infected with either RH or ME49 strains as well in non-infected cells in all analyzed times of infection. Also, the cell S phase indices were higher in ME49 strain-infected BeWo and HeLa cells as compared to non-infected controls and RH strain-infected cells. These results indicate that RH and ME49 strains of T. gondii possess opposing mechanism of interference in apoptosis and cell cycle S phase of both BeWo and HeLa cells and these differences can be associated to evasion strategies of the parasite to survive inside the host cells.

Do the placental barrier, parasite genotype and Toll-like receptor polymorphisms contribute to the course of primary infection with various Toxoplasma gondii genotypes in pregnant women?

“…Another study reported that BeWo choriocarcinoma cells went into apoptosis after infection with type II rather than type I strains. In this case, host cell death versus parasite death might reflect differential strain abilities to infect the placenta with varying degrees of virulence [21]. …”

Strain-Dependent Host Transcriptional Responses to Toxoplasma Infection Are Largely Conserved in Mammalian and Avian Hosts

“…Interestingly, the success of these strategies in murine hosts appears to vary dramatically by parasite strain. Strain-dependence has been observed for a range of phenotypes including blockade of host apoptosis [6], evasion of p47 GTPase-mediated killing [7], production of IL-12 [8], intersection of MAPK signaling [9], induction of NF-κB signaling [10], and induction and sustenance of JAK/STAT signaling [11]. It is therefore not surprising that where specific parasite effectors underlying these phenotypes have been identified and characterized, they are either highly polymorphic between different parasite strains [11], [12], [13] and/or differentially expressed between strains [9], [14], [15].…”

Tissue Barriers of the Human Placenta to Infection with Toxoplasma gondii

“…Alternatively, parasites may invade at the decidua-EVT interface, which occupies less than 5% of the maternal-fetal interface (Fig. 1B) (10).Almost all experimental T. gondii infections of the placenta have been performed in mice (6,24,34,54,63), sheep (16), or isolated trophoblast cells (4,7,34,52,55,56). However, none of these models accurately represent the architecture of the human placenta (reviewed in references 43 and 46).…”