Team Maps Infection Pathways in the Human Placenta

Researchers from the Wellcome Sanger Institute, the University of Cambridge, the University of Dundee, and collaborators have created a panoramic view of infection pathways in the human placenta. This remarkable achievement could pave the way for the development of pregnancy-safe therapies for malaria, toxoplasmosis, and listeria—diseases that can cause severe pregnancy complications.

Utilizing novel mini placenta models, the researchers mapped the placental response to infections during early development. This work is part of the broader Human Cell Atlas consortium, which aims to map every cell type in the human body to transform our understanding of health and disease.

The study, published in Cell Systems, focused on the pathways involved in malaria, toxoplasmosis, and listeria infection. It revealed that secondary inflammation might be the cause of pregnancy complications during these infections and uncovered that placental immune cells, known as Hofbauer cells, are likely to play a defensive role against pathogens.

Future work focusing on identifying potential drug targets in the pathways that cause complications during infection could inform the design of more directed therapies to tackle infections in early-stage pregnancies. This is particularly crucial in regions where these infections are more common, such as Sub-Saharan Africa and parts of Southeast Asia.

Despite the significant impact of infections during pregnancy, the pathways and mechanisms these infections use to cross the placenta have been poorly understood, partly due to the limitations of laboratory models and differences between humans and mice. The mini placenta models developed by this team can be used in future research to gain more insights into placental response to infections and wider placental changes during development.

According to Regina Hoo, co-first author from the Wellcome Sanger Institute, “While infections during pregnancy have been known to cause complications, including miscarriage and stillbirth, very little has been known about the underlying mechanisms. Our research shows that even with pathogens that cannot cross the placenta, the secondary inflammation from the immune system may be responsible for disrupting fetal development. Identifying key processes involved with the inflammation pathway could help us develop pregnancy-specific treatments that minimize this in the future.”