Research has shown that fetuses are not as vulnerable as previously believed; they can actually combat infections while still in the womb. This revelation may alter the approach doctors take to safeguard fetuses from infections that could result in serious health issues, such as microcephaly, a condition characterized by a head size significantly smaller than expected for the baby’s age.
Recent findings from Duke-NUS Medical School have uncovered that fetuses are not as defenseless as once imagined; they possess the ability to combat infections from within the womb. This new perspective could drastically impact how medical professionals shield fetuses from infections leading to significant health conditions, including microcephaly, which is marked by an unusually small head size for a baby’s age.
Published in the journal Cell, the study indicates that fetuses have an active immune system capable of fighting infections affecting their developing nervous system long before they are born. It was previously believed that only the mother’s immune system offered protection against infections for a fetus. This groundbreaking finding may provide significant benefits for women who experience infections during pregnancy. Congenital disorders, including those transmitted from mothers to fetuses during gestation, lead to approximately 240,000 newborn deaths each year.
Associate Professor Ashley St John from the Programme in Emerging Infectious Diseases at Duke-NUS, who led the study, stated:
“In the early stages of pregnancy, a fetus is unable to survive independently, leading to the assumption that it largely depends on the mother’s immune system for infection defense. However, our research reveals that a fetus’s immune system can begin to respond to infections much earlier than we previously thought.”
To explore this further, the researchers examined the fetal immune response using various strains of the Zika virus in a preclinical model. They observed that immune cells reacted differently to infections — some played a protective role, reducing damage to the developing brain, while others caused harmful inflammation that could injure the fetus’s brain.
The study also provided new insights into the function of microglia, a type of immune cell located in the brain. By using human brain models known as organoids or mini-brains, the researchers validated that these cells are crucial for the fetus’s defense against pathogens during infections.
Additionally, the researchers studied monocytes, white blood cells that originate in the bone marrow. The team, which included A*STAR scientists, found that these cells were attracted to the fetal brain during infections but also initiated harmful inflammation that led to brain cell death rather than eliminating the virus. It had been previously established that monocytes’ damaging effects primarily occur after birth, but this study demonstrated that they can also harm a developing fetal brain in utero.
Moreover, monocytes generate reactive molecules called reactive oxygen species, which assist the body in fighting pathogens by signaling other cells. However, the researchers found that a specific inflammatory signal, nitric oxide synthase-2 (NOS2), was released excessively, resulting in neuron damage when combined with large amounts of reactive oxygen species. Similar to how excessive bleach can ruin fabric, unregulated immune responses can also harm a fetus’s brain.
Based on these findings, scientists applied an experimental anti-inflammatory drug to inhibit the NOS2 function, which decreased the harmful inflammation caused by monocytes in the brain and protected the fetal brain from the Zika virus’s damaging effects.
Assoc. Prof. St John remarked that this study offers a new viewpoint on combating congenital disorders from infections:
“Our research has demonstrated that fetal immune responses can either be protective or harmful. Understanding the roles of various immune cells in fetal immunity is key to improving pregnancy outcomes.”
“We aspire to determine the safety of this anti-inflammatory drug through further testing, aiming to develop it into an effective treatment for protecting fetuses from harmful brain inflammation,” she added.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, expressed:
“Globally, there are substantial efforts to map the diverse cells within our bodies and their roles in health and disease. By uncovering the complexities of our early immune responses, this research takes us closer to a deeper understanding of the human body, which may lead to innovative medical treatments.”
This new research aligns with Duke-NUS’ initiatives to enhance global health by integrating fundamental scientific research with practical applications to develop pioneering biomedical solutions.
