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• W2039921504 endingPage "e1003821" @default.
• W2039921504 startingPage "e1003821" @default.
• W2039921504 abstract "Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is bathed in maternal blood, and constitutes the main interface between fetus and mother. Syncytiotrophoblasts are exposed to pathogens circulating in maternal blood, and appear to have unique resistance mechanisms against microbial invasion. These are due in part to the lack of intercellular junctions and their receptors, the Achilles heel of polarized mononuclear epithelia. However, the syncytium is immune to receptor-independent invasion as well, suggesting additional general defense mechanisms against infection. The difficulty of maintaining and manipulating primary human syncytiotrophoblasts in culture makes it challenging to investigate the cellular and molecular basis of host defenses in this unique tissue. Here we present a novel system to study placental pathogenesis using murine trophoblast stem cells (mTSC) that can be differentiated into syncytiotrophoblasts and recapitulate human placental syncytium. Consistent with previous results in primary human organ cultures, murine syncytiotrophoblasts were found to be resistant to infection with Listeria monocytogenes via direct invasion and cell-to-cell spread. Atomic force microscopy of murine syncytiotrophoblasts demonstrated that these cells have a greater elastic modulus than mononuclear trophoblasts. Disruption of the unusually dense actin structure – a diffuse meshwork of microfilaments - with Cytochalasin D led to a decrease in its elastic modulus by 25%. This correlated with a small but significant increase in invasion of L. monocytogenes into murine and human syncytium. These results suggest that the syncytial actin cytoskeleton may form a general barrier against pathogen entry in humans and mice. Moreover, murine TSCs are a genetically tractable model system for the investigation of specific pathways in syncytial host defenses." @default.
• W2039921504 created "2016-06-24" @default.
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• W2039921504 date "2013-12-12" @default.
• W2039921504 modified "2023-10-16" @default.
• W2039921504 title "Placental Syncytium Forms a Biophysical Barrier against Pathogen Invasion" @default.
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• W2039921504 doi "https://doi.org/10.1371/journal.ppat.1003821" @default.
• W2039921504 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3861541" @default.
• W2039921504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24348256" @default.
• W2039921504 hasPublicationYear "2013" @default.
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