Home Medizin Studie lüftet das Geheimnis der neonatalen Neutropenie bei Neugeborenen

Studie lüftet das Geheimnis der neonatalen Neutropenie bei Neugeborenen

von NFI Redaktion

Neonates are much more vulnerable to infections compared to adults, with these infections potentially leading to serious health complications and even death.

One factor known to influence a newborn’s response to infection is neonatal neutropenia, where the child does not produce enough neutrophils, the first responders of the immune system. The underlying cause of this immune deficiency, significantly increasing a neonate’s susceptibility to infections, is largely unknown, leaving doctors with limited knowledge on how to prevent or treat it.

A new study in mice by researchers at Columbia University now suggests that many cases of neonatal neutropenia could be due to the suppression of the fetus’s blood-forming stem cells, a natural maternal mechanism that protects the placenta from inflammation but can make newborns vulnerable to infections if not reversed after birth.

„We still have much to learn about neonatal neutropenia, but this is an encouraging step forward in developing new treatment methods. Our results suggest that it may be more productive to counteract maternal factors that suppress fetal and neonatal hematopoietic stem cells, instead of trying to directly increase the production of these cells.“

Emmanuelle Passegué, PhD, Alumni Professor of Genetics and Development at Vagelos College of Physicians and Surgeons and Director of the Columbia Stem Cell Initiative at Columbia University

The Clinical Challenge

Infants with neonatal neutropenia may develop early-onset sepsis, a life-threatening infection, within the first 72 hours of life.

„Early sepsis is a major problem in term infants, but in preterm infants, it is even more dangerous, with very high mortality rates,“ says lead author Amélie Collins, MD, PhD, Assistant Professor of Pediatrics and attending neonatologist for these hospitalized infants.

Doctors use broad-spectrum antibiotics to treat infants with early-onset sepsis. However, antibiotics are not always effective and often lead to other complications. „A treatment that strengthens the immune system of these infants could have a significant impact,“ says Collins.

The prevailing theory of neonatal neutropenia suggests that fetuses and newborns with this condition lack the regenerative ability to produce a large number of neutrophils to fight infections.

„But what this actually means from a mechanistic perspective is unknown,“ says Collins. „Perinatal hematopoiesis is a poorly understood area of biology.“

Experiments and Results

To understand how neutropenia develops in infants, Collins and Passegué investigated using mouse models how fetal and neonatal hematopoietic stem cells respond to infection.

Adults with infections typically rely on emergency myelopoiesis, a rapid-response mechanism of hematopoietic stem cells that generates a large number of immune cells, including neutrophils.

Collins and Passegué discovered that while emergency myelopoiesis becomes functional early in fetal development – with fetal hematopoietic stem cells capable of producing neutrophils – the fetus does not activate it.

This indicated that an external factor suppresses fetal myelopoiesis. Therefore, the researchers sought and found a maternal factor – interleukin 10 or IL-10 – that prevents emergency myelopoiesis from being activated during fetal development. Collins and Passegué found that the absence of IL-10 can restore emergency myelopoiesis in the fetus and increase neonatal neutrophil production in a way that likely brings important clinical benefits.

„This is the crucial translational advance of our study,“ says Collins. „Now that we know fetal and neonatal stem cells can produce neutrophils and have identified IL-10 as one of the factors that suppress emergency myelopoiesis, we should be able to understand the mechanism and find places to intervene.“

Potential Implications and Future Directions

This discovery was also enabled by a second mouse model developed by the researchers, allowing them to track what happens to mouse pups after birth (as removing IL-10 from infected pregnant mice resulted in fetal death).

This second model showed that newborn pups can utilize emergency myelopoiesis pathways after birth and will be crucial for future studies.

„We can now learn more about how maternal IL-10 suppresses fetal hematopoietic stem cells and what signals release those inhibitions after birth to translate these exciting findings into effective therapy,“ says Passegué.


Columbia University Irving Medical Center

Journal Reference:

Collins, A., et al. (2024). Maternal inflammation regulates fetal emergency myelopoiesis. Cell. doi.org/10.1016/j.cell.2024.02.002.

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