Department of Pediatrics, University of California, San Francisco, California, United States of America.
PLoS Pathog. 2010 Jan 22;6(1):e1000732. doi: 10.1371/journal.ppat.1000732.
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.
李斯特菌是导致母婴感染的一个重要原因，同时也是研究这些重要但尚未完全了解的事件的模式生物。李斯特菌可以通过两种方式感染非吞噬细胞：直接入侵和细胞间传播。每种方法对胎盘感染的相对贡献存在争议，入侵的解剖部位也是如此。在这里，我们首次报告了使用妊娠早期胎盘器官培养物来定量分析李斯特菌感染人类胎盘的情况。与之前的报告相反，我们发现，构成胎盘表面大部分并被母体血液浸润的合体滋养层对李斯特菌的感染具有很强的抵抗力，无论是通过内毒素介导的入侵还是细胞间传播。相反，绒毛外滋养层——将胎盘锚定在蜕膜（子宫内层）中，并大量表达 E-钙黏蛋白——成为李斯特菌从细胞外和细胞内环境进入的主要门户。随后，细菌向绒毛间质（胎儿毛细血管所在的位置）的传播受到进一步的细胞和组织学屏障的阻碍。我们的研究表明，胎盘已经进化出多种机制来抵抗病原体感染，尤其是来自母体血液的感染。这些发现为为什么几乎所有的胎盘病原体都具有细胞内生命周期提供了一个新的解释：它们可能需要母体细胞到达蜕膜并感染胎盘。
