Invasive Extravillous Trophoblasts Restrict Intracellular Growth and Spread of Listeria monocytogenes
Open Access
- 3 March 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 7 (3), e1002005
- https://doi.org/10.1371/journal.ppat.1002005
Abstract
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. Infection of the placenta and fetus is an important cause of pregnancy complications and fetal and neonatal morbidity and mortality. Listeria monocytogenes is an intracellular bacterial pathogen that causes pregnancy-related infections in humans. The pathogenesis of listeriosis during pregnancy is poorly understood. We have previously shown that transmission of L. monocytogenes from maternal cells and tissues to fetal cells occurs in the uterine implantation site, and that a small subpopulation of specialized fetal cells called extravillous trophoblasts are the preferred initial site of infection. Here we use primary human placental organ and cell culture systems to characterize the intracellular fate of L. monocytogenes in extravillous trophoblasts. We found that these cells entrap bacteria in vacuolar compartments where they are degraded and therefore reduce bacterial dissemination into deeper structures of the placenta. Our study provides new insights into the nature of the maternal-fetal barrier. Extravillous trophoblasts that are accessible to infection with intracellular pathogens from infected maternal cells have host defense mechanisms that constitute a bottleneck in maternal-fetal transmission.Keywords
This publication has 79 references indexed in Scilit:
- Inhibition of Listeria monocytogenes infection by neurological drugsInternational Journal of Antimicrobial Agents, 2010
- Perturbation of vacuolar maturation promotes listeriolysin O-independent vacuolar escape duringListeria monocytogenesinfection of human cellsCellular Microbiology, 2009
- Interferon Gamma in Successful Pregnancies1Biology of Reproduction, 2009
- Life on the inside: the intracellular lifestyle of cytosolic bacteriaNature Reviews Microbiology, 2009
- Chapter 12 Placental Remodeling of the Uterine VasculatureMethods in Enzymology, 2008
- GILT is a critical host factor for Listeria monocytogenes infectionNature, 2008
- Autophagosome formation: core machinery and adaptationsNature, 2007
- The cell biology ofListeria monocytogenesinfectionThe Journal of cell biology, 2002
- Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes.The Journal of cell biology, 1989
- Role of hemolysin for the intracellular growth of Listeria monocytogenes.The Journal of Experimental Medicine, 1988