Early infection response of the first trimester human placenta at single-cell scale
Early infection response of the first trimester human placenta at single-cell scale
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DOI：
10.1101/2023.01.02.522155
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发表时间：
2023-01
期刊：
影响因子：
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通讯作者：
R. Hoo;E. Ruiz-Morales;I. Kelava;Carmen Sancho-Serra;C. Mazzeo;Sara Chelaghma;E. Tuck;A. Predeus-A.-Pr
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作者：
R. Hoo;E. Ruiz-Morales;I. Kelava;Carmen Sancho-Serra;C. Mazzeo;Sara Chelaghma;E. Tuck;A. Predeus-A.-Pr
胎盘感染是世界范围内的主要负担，特别是在发展中国家。胎盘是位于母亲和胎儿交界处的临时组织。一些病原体可以进入胎盘屏障，导致从母亲到胎儿的病理性传播，这可能会对发育中的胎儿的健康产生深远的影响。有限的组织可及性，人类和小鼠之间的关键差异，以及直到最近，缺乏适当的体外模型，都阻碍了我们对病原体早期胎盘反应的理解。在这里，我们使用单细胞转录组来描述胎盘对三种已知在怀孕期间导致胎儿和母体并发症的病原体的初级防御机制-恶性疟原虫、单核细胞增多性李斯特菌和弓形虫。我们对妊娠早期胎盘的体外移植进行了优化，发现滋养细胞(胎盘的上皮样细胞)和霍夫鲍尔细胞(胎盘巨噬细胞)在感染24小时后协调了炎症反应。我们发现，在滋养层细胞中，激素的生物合成和运输被下调，这表明保护性反应的促进是以降低胎盘的其他关键功能为代价的，如内分泌产生和胎儿的营养。此外，我们准确地指出了病原体在某些胎盘谱系中的特定作用，包括弓形虫对Hofbauer细胞的强烈线粒体改变。最后，我们确定了适应策略，并验证了恶性疟原虫在胎盘疟疾感染过程中所使用的营养获取。这项研究提供了妊娠早期胎盘感染时的第一张详细的细胞图，并描述了如果不加检查可能导致胎儿和胎盘紊乱的早期事件。
Placental infections are a major worldwide burden, particularly in developing countries. The placenta is a transient tissue located at the interface between the mother and the fetus. Some pathogens can access the placental barrier resulting in pathological transmission from mother to fetus, which may have a profound impact on the health of the developing fetus. Limited tissue accessibility, critical differences between humans and mice, and, until recently, lack of proper in vitro models, have hampered our understanding of the early placental response to pathogens. Here we use single-cell transcriptomics to describe the placental primary defence mechanisms against three pathogens that are known to cause fetal and maternal complications during pregnancy - Plasmodium falciparum, Listeria monocytogenes and Toxoplasma gondii. We optimise ex vivo placental explants of the first-trimester human placenta and show that trophoblasts (the epithelial-like cells of the placenta), and Hofbauer cells (placental macrophages) orchestrate a coordinated inflammatory response after 24 hours of infection. We show that hormone biosynthesis and transport are downregulated in the trophoblasts, suggesting that protective responses are promoted at the expense of decreasing other critical functions of the placenta, such as the endocrine production and the nourishment of the fetus. In addition, we pinpoint pathogen-specific effects in some placental lineages, including a strong mitochondrial alteration in the Hofbauer cells in response to T. gondii. Finally, we identify adaptive strategies and validate nutrient acquisition employed by the P. falciparum during placental malaria infection. This study provides the first detailed cellular map of the first-trimester placenta upon infection and describes the early events that may lead to fetal and placental disorders if left unchecked.