CANCELLED Early infection response of the first-trimester placenta at single cell resolution

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• Dr Roser Vento-Tormo (Wellcome Sanger Institute)
• Wednesday 05 April 2023, 16:00-17:00
• Seminar Room, Tennis Court Road, Dept of Pathology..

If you have a question about this talk, please contact Anna Protasio.

This is a hybrid talk. You can attend in person or via zoom. See abstract for details

The placenta functions as a selective barrier located at the interface between the mother and the fetus, supporting fetal nutrition and protection against pathological infections during pregnancy. However, some pathogens can attach and even cross the placenta, causing pregnancy complications which in some cases can have lifelong impacts on the child’s health. Infections during pregnancy are a major burden worldwide but have been poorly studied owing to limited tissue availability. Here, we optimise ex vivo first-trimester placental explants to generate the first single-cell census of placental infection, focusing on three pathogens associated with intrauterine complications – Plasmodium falciparum, Listeria monocytogenes and Toxoplasma gondii. We demonstrate that the trophoblasts, the specialised epithelial cells of the placenta, mount an inflammatory response that compromises placental function. The transcriptomic programme of trophoblasts during infection resembles that of pre-eclampsia, including the characteristic over-expression of angiogenic genes. Trophoblasts also upregulate chemokines that recruit both Hofbauer cells (fetal primitive macrophages in the placenta) and maternal macrophages (monocyte-derived macrophages attached to the placenta) to the site of infection. We show that independent of their origin, both fetal and maternal macrophages play an active role in the local inflammatory response. Finally, we sequenced the transcriptome of pathogens infecting the trophoblast and discovered a metabolic adaptation of P. falciparum to the placental environment, which we validated experimentally. This study provides the first detailed cellular map of the first-trimester human placenta upon infection, and sheds new light on the early innate inflammatory mechanisms that may lead to maternal and placental disorders if left unchecked.

We encourage in person attendance but the talk will also be streamed via zoom

This talk is part of the Parasitology Seminars series.

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