Researchers from the Wellcome Sanger Institute, the University of Cambridge, the University of Dundee, and collaborators have created the first panoramic view of infection pathways in the human placenta. This could help identify potential drug targets for developing pregnancy-safe therapies for diseases such as malaria, toxoplasmosis, and listeria, which can all lead to severe pregnancy complications. The study mapped the placenta’s response to infections from these diseases in high resolution, potentially opening up new treatment options. The team used novel ‘mini placenta’ techniques in their research.models for understanding the placental response to early development infections. This research is a part of the larger Human Cell Atlas consortium1, which seeks to map every cell type in the human body to revolutionize our knowledge of health and disease.
The research, released today (3 May) in Cell Systems, concentrated on the pathways linked to malaria, toxoplasmosis, and listeria infection, all of which can lead to complications during pregnancy and miscarriage. It found that secondary inflammation could be the reason for pregnancy complications during these infections and revealed that placental immune cells are likely to have a defensive role.
Research is being conducted to find potential drug targets in the pathways that cause complications during infections in early-stage pregnancies.
Infections during pregnancy are a significant global health issue, impacting millions of people worldwide. These infections can lead to maternal death, sepsis, and pregnancy complications such as miscarriage, fetal developmental issues, low birth weight, and stillbirth. Malaria, toxoplasmosis, and listeria are common infections that can pose a threat during pregnancy.
pregnancy due to the potential for serious complications from these infections, especially in regions with a higher prevalence of the diseases. For instance, in areas like Sub-Saharan Africa and parts of Southeast Asia where the malaria parasite Plasmodium falciparum is widespread, the risk is particularly high.
The placenta serves as a protective barrier during pregnancy, allowing essential nutrients to pass from the mother to the baby while preventing harmful pathogens and toxins from crossing. However, the pathogens that lead to toxoplasmosis and listeria can breach the placenta, and the malaria parasite can attach to its exterior. As a result, the fetus is at a heightened risk of harm.At the beginning of development, the immune response is not fully formed, so the fetus depends on the placental barrier for protection. Infections during pregnancy can have a significant impact, but the ways in which these infections cross the placenta are not well understood. This is partly because of the limitations of laboratory models and the differences between humans and mice. In a recent study from the Wellcome Sanger Institute and collaborators, the team used “mini placentas” from human samples to study the response to infection at the individual level.
Researchers have discovered a type of fetal immune cell called a Hofbauer cell, which is activated in all three types of infections but in different ways. This is the first time that immune cells in the placenta have been shown to have a defensive role against pathogens in a model of the human placenta.
The team also found that pathogens can penetrate these immune cells. For example, the parasite T. gondii, which causes toxoplasmosis, is likely to use these immune cells to avoid the ongoing immune response and spread throughout the body.
Additionally, the researchers found that all three infections induced a general e-cell resolution.The placenta’s dysregulated functions might be due to an inflammatory response, indicating that certain pregnancy complications could be caused by secondary inflammation. Targeting these inflammation pathways could potentially result in pregnancy-specific treatment for infections, which is not currently available. The ‘mini placenta’ models created by the team could be used in future research to gain a better understanding of the placental response to infections and broader changes during development. Dr. Regina Hoo, a co-first author from the Wellcome Sanger Institute, mentioned, “While Infections that occur during pregnancy can lead to complications such as miscarriage and stillbirth, but the exact reasons behind this have not been well understood. Our study reveals that even when pathogens are unable to cross the placenta, the resulting secondary inflammation from the immune system could potentially disrupt the development of the fetus. By identifying the specific processes involved in this inflammatory pathway, we may be able to develop treatments tailored to pregnancy that can minimize this risk in the future.”
Elias Ruiz-Morales, co-first author from the Wellcome Sanger Institute, stated: The placental immune cells have been found to protect the placenta against infections during early-stage pregnancy in humans. This is the first time that such a defensive role has been discovered. These immune cells can also be exploited by toxoplasma during infection. Understanding more about the placental immune system’s functioning can provide new insights into pregnancy complications. Dr. Marcus Lee, co-senior author from the Wellcome Sanger Institute, now at the University of Dundee, emphasized the importance of understanding how the parasite adapts during infection and how the body responds, especially since millions of pregnancies are potentially exposed to malaria each year.
“The Human Cell Atlas (HCA) consortium is dedicated to mapping every cell type in the human body to improve our understanding of human health and to help diagnose, monitor, and treat disease. It is a global, scientist-led effort with over 3,400 members from 101 countries, involving researchers, institutes, and funders. The consortium’s goal is to create a comprehensive and open resource for the scientific community.”
This information is sourced from various articles and reports including:
- Seale, A. (2020) Recognising the burden of maternal infection worldwide, The Lancet, DOI: 10.1016/S2214-109X(20)30126-1
- Chan MY, Smith MA. (2018) Infections in Pregnancy. Comprehensive Toxicology. DOI: 10.1016/B978-0-12-801238-3.64293-9
- World Health Organization, World Malaria Report 2023
All tissue samples were obtained with written informed consent from all participants in accordance with ethics guidelines and regulations.
