Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts—which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin—served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta.

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...

The average domain size determined from pXRD is 10 nm. The particles have been characterized by pXRD, SEM, STEM, EDX, and CBED. SEM and STEM images show the particles to be aggregated, forming clusters and chains. The BET surface area of the nanoparticles was measured using Kr as the adsorbing gas. The electrocatalytic oxidation of formic acid and methanol by the as-prepared PtPb and PtBi nanoparticles has been studied by rotating disk voltammetry for potential fuel-cell applications. The PtPb and PtBi nanoparticles displayed enhanced electrochemical activity toward formic acid and methanol oxidation when compared to commercially available Pt and PtRu nanoparticles. The electrocatalytic activity of the PtPb nanoparticles was studied as a function of sonication time of the catalyst ink, and morphology changes were followed by scanning electron microscopy. The results showed that the activity of the catalyst initially increased with sonication time and then decreased.

Intermetallic PtPb nanoparticles have been synthesized by two solution-phase reduction methods. In the first (PtPb-B), Pt and Pb salts were reduced by sodium borohydride in methanol at room temperature. In the second (PtPb-N), metal-organic Pt and Pb precursors were reduced by sodium naphthalide in diglyme at 135 degrees C. Both methods produced small agglomerated nanoparticles of the ordered intermetallic PtPb (mean crystal domain size <15 nm) which were characterized by pXRD, SEM, UHV-STEM, BET, EDX, and electron diffraction. The electrocatalytic activity of PtPb nanoparticles produced by both methods toward formic acid and methanol oxidation was investigated and compared to Pt and PtRu. Both PtPb-B and PtPb-N nanoparticles exhibited enhanced electrocatalytic activity compared to commercially available Pt black and PtRu nanoparticles. For formic acid oxidation, the PtPb nanoparticles exhibited considerably lower onset potentials and higher current densities than Pt or PtRu. For methanol oxidation, the PtPb nanoparticles had onset potentials slightly positive of PtRu but exhibited higher current densities at potentials about 100 mV positive of onset. The general applicability of these methods for the synthesis of nanoparticles of ordered intermetallic phases is discussed.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that can infect the placenta, a chimeric organ made of maternal and fetal cells. Extravillous trophoblasts (EVT) are specialized fetal cells that invade the uterine implantation site, where they come into direct contact with maternal cells. We have shown previously that EVT are the preferred site of initial placental infection. In this report, we infected primary human EVT with L. monocytogenes. EVT eliminated ∼80% of intracellular bacteria over 24-hours. Bacteria were unable to escape into the cytoplasm and remained confined to vacuolar compartments that became acidified and co-localized with LAMP1, consistent with bacterial degradation in lysosomes. In human placental organ cultures bacterial vacuolar escape rates differed between specific trophoblast subpopulations. The most invasive EVT—those that would be in direct contact with maternal cells in vivo—had lower escape rates than trophoblasts that were surrounded by fetal cells and tissues. Our results suggest that EVT present a bottleneck in the spread of L. monocytogenes from mother to fetus by inhibiting vacuolar escape, and thus intracellular bacterial growth. However, if L. monocytogenes is able to spread beyond EVT it can find a more hospitable environment. Our results elucidate a novel aspect of the maternal-fetal barrier.