Tissue Barriers of the Human Placenta to Infection with Toxoplasma gondii

Abstract

Toxoplasma gondii is a ubiquitous, obligate intracellular parasite capable of crossing the placenta to cause spontaneous abortion, preterm labor, or significant disease in the surviving neonate. Exploration of the cellular and histological components of the placental barrier is in its infancy, and both how and where T. gondii breaches it are unknown. The human placenta presents two anatomical interfaces between maternal cells and fetal cells (trophoblasts): (i) the villous region where maternal blood bathes syncytialized trophoblasts for nutrient exchange and (ii) the maternal decidua, where mononuclear, extravillous trophoblasts anchor the villous region to the uterus. Using first-trimester human placental explants, we demonstrate that the latter site is significantly more vulnerable to infection, despite presenting a vastly smaller surface. This is consistent with past findings concerning two vertically transmitted viruses and one bacterium. We further explore whether three genetically distinct T. gondii types (I, II, and III) are capable of preferential placental infection and survival in this model. We find no difference in these strains' ability to infect placental explants; however, slightly slower growth is evident in type II (Prugniaud [Pru]) parasites relative to other cell types, although this did not quite achieve statistical significance.T oxoplasma gondii is a ubiquitous parasite of human and veterinary medical importance. This obligate, intracellular protozoan undergoes the sexual portion of its life cycle in cats, the sole definitive host; it also has an asexual life cycle in a broad range of warm-blooded intermediate hosts, most significantly rodents, livestock, and humans. The main modes of transmission are therefore ingestion of oocysts shed in cat feces or of tissue cysts in undercooked meat from intermediate hosts. T. gondii is capable of crossing the blood-brain, blood-ocular, and maternal-fetal barriers. Thus, the vertical route from mother to fetus represents an additional mode of transmission. Fetal infection can cause spontaneous abortion, preterm labor, or significant neurological and ocular sequelae in the surviving offspring.Primary maternal infection during pregnancy is responsible for almost all fetal infection and its frequency depends on human seroprevalence rates that range from ϳ10 to 80% across nations (53). Prenatal testing for toxoplasmosis is routinely offered in many European countries, and drug therapy with spiramycin is prescribed after the diagnosis of maternal infection in order to prevent mother-to-child transmission (19). However, whether prenatal treatment has any effect on vertical transmission is unclear from the results of a systematic review of cohort studies because of numerous biases in the way these studies were designed (65). Randomized controlled clinical trials are needed to obtain evidence for the benefit of prenatal treatment.The mechanisms by which T. gondii infects the placenta and crosses from mother to fetus are poorly understood and experimentally co...

Concepts and Mechanisms: Crossing Host Barriers

“…Tg has been shown to infect directly primary human trophoblasts (Abbasi et al 2003) and extravillous trophoblasts of human ex vivo inoculated placental explants (Robbins et al 2012), as well as trophoblasts in a rodent animal model (Calomys callosus) (Ferro et al 2002). This invasion may be the critical event leading to the infection of the fetus.…”

Lipid Raft- and Src Family Kinase-Dependent Entry of Coxsackievirus B into Human Placental Trophoblasts

“…As the trophoblast is likely the initial site of pathogen invasion across the placenta (29)(30)(31); further reviewed in reference 32), we modeled CVB entry into cytotrophoblasts using an undifferentiated human BeWo trophoblast cell line and complemented our findings using cultures of primary human trophoblasts. We show that the kinet-ics of CVB entry and uncoating in placental trophoblasts are similar to those previously described in polarized intestinal epithelial cells.…”

Congenital Toxoplasmosis

“…For untreated women, the transmission rate is approximately 25 percent in the first trimester, 54 percent in the second trimester, and 65 percent in the third trimester. Although the precise mechanism of movement of the parasite across the human placental is not fully understood, recent studies may offer new insights [5]. Human placental studies suggest that the extravillous trophoblasts (EVT) that anchor the placenta to the uterus are much more vulnerable to infection than are the syncytiotrophoblasts that are bathed in maternal blood [5].…”

“…Although the precise mechanism of movement of the parasite across the human placental is not fully understood, recent studies may offer new insights [5]. Human placental studies suggest that the extravillous trophoblasts (EVT) that anchor the placenta to the uterus are much more vulnerable to infection than are the syncytiotrophoblasts that are bathed in maternal blood [5]. Studies in animals have shown that initial infection occurs in the uterus [5].…”