SINGAPORE: Research from Duke-NUS Medical School has found that foetuses have a functional immune system capable of fighting infections while still in the womb. This revelation challenges the long-held belief that foetuses are entirely dependent on their mothers’ immune systems for protection.
The study, published in Cell, has the potential to reshape how doctors approach the prevention of serious health conditions like microcephaly, where a baby’s head is abnormally small due to infection-related brain damage during pregnancy.
For years, it was believed that a foetus’ immune system was too underdeveloped to respond to infections. Instead, protection was thought to come solely from the mother’s immune response. However, the research led by Associate Professor Ashley St John from Duke-NUS’s Programme in Emerging Infectious Diseases suggests that foetuses possess a more robust immune defence than previously understood.
This new insight could be pivotal for pregnant women who contract infections, which are responsible for approximately 240,000 newborn deaths worldwide each year due to congenital disorders.
Assoc Prof St John explained, “Early in pregnancy, a foetus cannot survive on its own, and we have always assumed that it mostly relies on the mother’s immune system for protection against infections. However, we found that the foetus’ own immune system is already able to mount defences against infections much earlier than previously thought.”
In their study, the researchers used a preclinical model to observe foetal immune responses to Zika virus strains from various regions. Their findings revealed that the foetal immune system behaves in complex ways: while some immune cells help protect the developing brain from infection, others can contribute to harmful inflammation, which damages the brain.
A particularly important discovery came from examining microglia, immune cells in the brain, using human brain organoids (miniature brain models). These cells play a critical protective role during infection, highlighting their importance in the foetal immune system’s defence against pathogens.
Additionally, the team investigated monocytes, which are white blood cells produced in the bone marrow. Their research revealed that while monocytes can fight infection, they can also trigger harmful inflammation, leading to brain damage before birth. This was a notable finding, as it was previously thought that the damaging effects of monocytes only became apparent after birth.
The researchers found that monocytes, in their attempt to combat infection, release reactive oxygen species (ROS)—highly reactive molecules that help cells detect pathogens. However, when combined in excess with a specific inflammatory signal called nitric oxide synthase-2 (NOS2), these ROS can damage neurons in the developing foetal brain. This highlights the delicate balance the immune system must maintain to avoid harm.
In response to these findings, the researchers tested an experimental anti-inflammatory drug designed to block NOS2. This treatment reduced the harmful inflammation caused by monocytes and helped protect the foetal brain from the damage typically caused by Zika infections.
Assoc Prof St John expressed hope that this breakthrough could lead to new treatments for preventing brain damage in foetuses, saying, “Our work has shown that the immune responses of foetuses can be either protective or harmful. Knowing how various immune cells contribute to foetal immune protection will be important in our continued search for ways to improve pregnancy outcomes.”
The study’s findings also shed light on the intricate immune processes that occur early in development, bringing researchers closer to understanding how our bodies respond to health threats.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, added, “By revealing the intricacies of our earliest immune responses, this study brings us a step closer to having a more comprehensive understanding of the human body’s inner workings, potentially paving the way for new medical interventions.”
As research progresses, there is hope that these insights will lead to safer and more effective treatments to protect foetuses from harmful infections, ultimately reducing the risks of congenital diseases and improving outcomes for pregnant women and their babies.