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SUMMARY:CANCELLED Early infection response of the first-trimester placenta
  at single cell resolution - Dr Roser Vento-Tormo (Wellcome Sanger Institu
 te)
DTSTART:20230405T150000Z
DTEND:20230405T160000Z
UID:TALK192704@talks.cam.ac.uk
CONTACT:Anna Protasio
DESCRIPTION:The placenta functions as a selective barrier located at the i
 nterface between the mother and the fetus\, supporting fetal nutrition and
  protection against pathological infections during pregnancy. However\, so
 me pathogens can attach and even cross the placenta\, causing pregnancy co
 mplications 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 optim
 ise ex vivo first-trimester placental explants to generate the first singl
 e-cell census of placental infection\, focusing on three pathogens associa
 ted with intrauterine complications - Plasmodium falciparum\, Listeria mon
 ocytogenes and Toxoplasma gondii. We demonstrate that the trophoblasts\, t
 he specialised epithelial cells of the placenta\, mount an inflammatory re
 sponse that compromises placental function. The transcriptomic programme o
 f trophoblasts during infection resembles that of pre-eclampsia\, includin
 g the characteristic over-expression of angiogenic genes. Trophoblasts als
 o upregulate chemokines that recruit both Hofbauer cells (fetal primitive 
 macrophages in the placenta) and maternal macrophages (monocyte-derived ma
 crophages 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 th
 e transcriptome of pathogens infecting the trophoblast and discovered a me
 tabolic adaptation of P. falciparum to the placental environment\, which w
 e validated experimentally. This study provides the first detailed cellula
 r map of the first-trimester human placenta upon infection\, and sheds new
  light on the early innate inflammatory mechanisms that may lead to matern
 al and placental disorders if left unchecked.\n\nWe encourage in person at
 tendance but the talk will also be streamed via "zoom":https://zoom.us/j/9
 2211019683?pwd=ZUY4eHRaMkxKT3I0b215SlVtMlkwQT09
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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