Department of Microbiology and Molecular Genetics, Michigan State Universitygrid.17088.36, East Lansing, Michigan, USA.
Institute of Quantitative Health Sciences and Engineering, Michigan State Universitygrid.17088.36, East Lansing, Michigan, USA.
Infect Immun. 2022 Oct 20;90(10):e0034722. doi: 10.1128/iai.00347-22. Epub 2022 Sep 26.
Placental immunity is critical for fetal health during pregnancy, as invading pathogens spread from the parental blood to the fetus through this organ. However, inflammatory responses in the placenta can adversely affect both the fetus and the pregnant person, and the balance between protective placental immune response and detrimental inflammation is poorly understood. Extracellular vesicles (EVs) are membrane-enclosed vesicles that play a critical role in placental immunity. EVs produced by placental trophoblasts mediate immune tolerance to the fetus and to the placenta itself, but these EVs can also activate detrimental inflammatory responses. The regulation of these effects is not well characterized, and the role of trophoblast EVs (tEVs) in the response to infection has yet to be defined. The Gram-positive bacterial pathogen Listeria monocytogenes infects the placenta, serving as a model to study tEV function in this context. We investigated the effect of L. monocytogenes infection on the production and function of tEVs, using a trophoblast stem cell (TSC) model. We found that tEVs from infected TSCs can induce the production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in recipient cells. Surprisingly, this tEV treatment could confer increased susceptibility to subsequent L. monocytogenes infection, which has not been reported previously as an effect of EVs. Proteomic analysis and RNA sequencing revealed that tEVs from infected TSCs had altered cargo compared with those from uninfected TSCs. However, no L. monocytogenes proteins were detected in tEVs from infected TSCs. Together, these results suggest an immunomodulatory role for tEVs during prenatal infection.
胎盘免疫对于怀孕期间胎儿的健康至关重要，因为病原体通过胎盘从母体血液传播到胎儿。然而，胎盘的炎症反应会对胎儿和孕妇产生不利影响，而保护性胎盘免疫反应和有害炎症之间的平衡还知之甚少。细胞外囊泡（EVs）是一种膜包裹的囊泡，在胎盘免疫中发挥着关键作用。胎盘滋养细胞产生的 EVs 介导对胎儿和胎盘本身的免疫耐受，但这些 EVs 也可以激活有害的炎症反应。这些效应的调节机制尚不清楚，滋养细胞 EVs（tEVs）在感染反应中的作用尚未确定。革兰氏阳性细菌病原体李斯特菌感染胎盘，可作为研究 tEV 在这种情况下功能的模型。我们使用滋养细胞干细胞（TSC）模型研究了李斯特菌感染对 tEV 产生和功能的影响。我们发现，来自感染 TSC 的 tEV 可以诱导受体细胞中促炎细胞因子肿瘤坏死因子-α（TNF-α）的产生。令人惊讶的是，这种 tEV 处理可以使细胞对随后的李斯特菌感染更易感染，这以前从未被报道为 EV 的作用。蛋白质组学分析和 RNA 测序显示，与未感染 TSC 的 tEV 相比，感染 TSC 的 tEV 具有改变的货物。然而，在感染 TSC 的 tEV 中未检测到李斯特菌蛋白。总之，这些结果表明 tEVs 在产前感染期间具有免疫调节作用。
