Summary: New research has demonstrated that fetuses may develop immune responses to infections long before delivery, refuting the notion that they merely rely on parental immunity. A research on Zika virus infection found that immune cells like microglia protect the developing brains, while others, like monocytes, may produce harmful disease.
Researchers demonstrated that using an experimental drug to combat damaging inflammation can protect the fetal brain. This development opens up new strategies for preventing inherited diseases and treating infections while pregnant.
Important Information:
- Fetal Immunity: Babies have a practical defensive system capable of combating infections first in development.
- Protective vs. Harmful: Microglia protect the head, but macrophages may cause irritation that damages fetal cells.
- Medical Potential: Using experimental drugs to stop dangerous inflammatory responses could stop brain damage brought on by infections.
Origin: Duke NUS
According to the most recent study from Duke-NUS Medical School, fetuses may combat infections from within the womb as well as previously believed.
This new knowledge could have a significant impact on how doctors protect fetuses from serious health problems like idiocy, where the baby’s head is substantially smaller than expected for its time.
The researchers ‘ findings were made in the study, which was published in the journal Cell.
Prior research had demonstrated that a newborn ‘ immune system was the only defense against disease from the mother. This ground-breaking finding has the potential to be beneficial for pregnant women who develop diseases.
Congenital issues, including those caused by diseases transmitted from mothers to fetuses during childbirth, produce about 240, 000 kid deaths annually.
Associate Professor Ashley St John , from the Programme in Emerging Infectious Diseases at Duke-NUS, the lead author on the research, said:
” Early in pregnancy, a fetus cannot live on its own, and we have always assumed that it mostly relies on the family’s immune system for protection against infection. However, we discovered that the infant ‘ own immune system can develop defenses against pathogens much sooner than previously believed.
Further investigation was conducted by the researchers using Zika virus strains from all over the universe to study the maternal immune response in a preliminary model. They discovered that immune cells have different reactions to infection, either playing a protective role and preventing harm to the developing brains of the newborn, or acting as a deterrent to non-protective inflammation.
The study revealed fresh insights into the function of the brain’s microglia, a specific type of defense body. The researchers found that organoids or minibrains, which are found in human brains designs, play a protective role in the development of fetal immunity against bacteria.
Monocytes, white blood cells produced in the bone marrow, were another type of defensive body that the experts studied.
The group, which included A*STAR researchers, found that besides being drawn to the fetal head during an illness, they triggered harmful swelling in the head, killing brain cells instead of eliminating the disease.
While it was previously believed that monocytes have a harmful effect only after birth, this finding revealed that these immune cells can also harm a developing foetal brain before birth.
Additionally, monocytes produce highly reactive molecules known as reactive oxygen species, which aid in the body’s defense against pathogens by triggering the release of inflammatory signals from cells when they are alerted to a pathogen.
However, the researchers found that a particular inflammatory signal called nitric oxide synthase-2 ( NOS2 ), which when combined with reactive oxygen species in large quantities, caused neuron damage.
If immune responses are not properly controlled, they can harm a fetus ‘ brain just as much as bleach can damage a piece of clothing when used in excess.  ,  ,  ,
The scientists used an experimental anti-inflammatory drug to block the function of NOS2 in response to this finding. This prevented the foetal brain from the harm that Zika infections can cause by reducing the non-protective inflammation induced by monocytes in the brain.
Assoc Prof. St John praised the study’s fresh perspective on the fight against congenital infections:
” Our research has demonstrated that fetuse immune responses can be both protective and harmful,” says Dr. Nicolai. In our ongoing search for ways to improve pregnancy outcomes, it will be important to know how various immune cells contribute to fetal immune protection.
She added,” We hope that with further testing, we can establish the safety of the anti-inflammatory drug so that it can be developed into a workable method of treatment that protects fetuses from harmful inflammation in their brains.”
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, commented:
There are significant efforts underway to map the various cells in our bodies and how they affect human health and disease around the world.
This study “gives us a step closer to having a more thorough understanding of the inner workings of the human body, potentially paving the way for new medical interventions,” says the author. ”  ,
This fresh study is a part of Duke-NUS’s efforts to advance global health by bringing together fundamental scientific research and translational applications to create novel biomedical solutions.
About this information on research into neurodevelopment
Author: Brandon Raeburn
Source: Duke NUS
Contact: Brandon Raeburn – Duke NUS
Image: The image is credited to Neuroscience News
Original Research: Open access.
By Ashley St John and colleagues,” The contributions of fetal mononuclear phagocytes to neuroinvasion and neuroprotection during congenital infection” is a study. Cell
Abstract
fetal mononuclear phagocytes have different roles in neuroinvasion and neuroprotection during congenital infection.
Fetal immune cells perform their functions during congenital infections are poorly understood. ZIKV, a virus that can vertically transmit from a mother to a fetus, can infect the nervous system and lead to congenital ZIKV syndrome ( CZS ).
We found that fetal monocyte/macrophage cell types and microglia have different functional roles in the clearance of ZIKV from mouse models.
Trafficking of ZIKV-infected primitive macrophages from the yolk sac allowed initial fetal virus inoculation, while recruited monocytes promoted non-productive neuroinflammation.
Conversely, brain-resident differentiated microglia were protective, limiting infection and neuronal death. The contributions of mononuclear phagocyte subsets to their protective and harmful roles were identified by single-cell RNA sequencing.
Microglia also promoted infection clearance and neuroprotective transcriptional changes in human brain organoids. Thus, microglia are protective before birth, contrasting with the disease-enhancing roles of primitive macrophages and monocytes.
The potential of immune cells to influence various outcomes during fetal infections is demonstrated by the differential modulation of myeloid cell phenotypes by genetically different ZIKVs.
