Acute response to pathogens in the early human placenta at single-cell resolution

TY - JOUR

T1 - Acute response to pathogens in the early human placenta at single-cell resolution

AU - Hoo, Regina

AU - Ruiz-Morales, Elias R.

AU - Kelava, Iva

AU - Rawat, Mukul

AU - Mazzeo, Cecilia Icoresi

AU - Tuck, Elizabeth

AU - Sancho-Serra, Carmen

AU - Chelaghma, Sara

AU - Predeus, Alexander V.

AU - Murray, Simon

AU - Fernandez-Antoran, David

AU - Waller, Ross F.

AU - Álvarez-Errico, Damiana

AU - Lee, Marcus C. S.

AU - Vento-Tormo, Roser

N1 - Copyright: © 2024 The Authors

PY - 2024/5/15

Y1 - 2024/5/15

N2 - The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child's health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications—Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications.

AB - The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child's health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications—Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications.

KW - host-pathogen interactions

KW - immunology

KW - infections during pregnancy

KW - Listeria

KW - macrophages

KW - malaria

KW - placenta

KW - Plasmodium

KW - single-cell genomics

KW - Toxoplasma

UR - https://www.scopus.com/pages/publications/85192689441

U2 - 10.1016/j.cels.2024.04.002

DO - 10.1016/j.cels.2024.04.002

M3 - Article

C2 - 38703772

AN - SCOPUS:85192689441

SN - 2405-4712

VL - 15

SP - 425-444.e9

JO - Cell Systems

JF - Cell Systems

IS - 5

ER -