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

Area of Science:

• Reproductive biology
• Immunology
• Infectious diseases

Background:

• The placenta acts as a crucial maternal-fetal barrier, protecting against infections.
• Certain pathogens can breach this barrier, leading to severe pregnancy complications and long-term child health issues.

Purpose of the Study:

• To profile single-cell placental responses to Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii.
• To understand the cellular mechanisms underlying pregnancy complications caused by intrauterine infections.

Main Methods:

• Single-cell profiling of placental tissues.
• Analysis of cellular responses to specific pathogens.
• Characterization of Hofbauer cell (HBC) interactions with pathogens.

Main Results:

• All placental cell types initiate inflammatory responses upon pathogen exposure, potentially impairing placental function.
• Hofbauer cells (HBCs) were identified as a likely niche for Toxoplasma gondii.
• Plasmodium falciparum was observed to adapt by altering protein export and nutrient uptake within host erythrocytes.

Conclusions:

• Defined cellular networks and signaling pathways mediate acute placental inflammation in response to pathogens.
• These inflammatory responses may contribute significantly to pregnancy complications.
• Understanding these mechanisms is key to mitigating the impact of infections on maternal and child health.