Neutrophil Function and Immune Response in Neonatal Health

Neutrophils are central to the innate immune defence of newborns, providing the first line of protection against bacterial, viral and fungal invasion. In neonates, production, maturation and deployment of neutrophils—collectively termed granulopoiesis—undergo unique developmental regulation, yielding cells with distinct migratory, phagocytic and antimicrobial characteristics. Pre-term infants exhibit reduced neutrophil storage pools, impaired chemotaxis and attenuated degranulation, whereas term neonates show more mature profiles that continue to evolve in the early postnatal period. Rapid emergency granulopoiesis can be triggered by infection, but may be limited by immature bone-marrow niches. Neutrophil extracellular trap (NET) formation provides a non-phagocytic mechanism to immobilise pathogens, yet excessive NET release can provoke tissue injury and immunopathology. Neonatal immunity also favours a disease-tolerance strategy that limits inflammatory damage, in part through metabolic regulation of cytokine production and controlled neutrophil turnover. Interaction with the vascular endothelium, secretion of immunomodulatory mediators and cross-talk with monocytes and lymphocytes further shape the early-life immune landscape. Understanding these nuances has global significance, informing approaches to prevent and manage sepsis, optimise vaccine responses and tailor interventions in resource-limited settings.

Research from Nature Portfolio

Recent studies have revealed a critical regulatory axis that sustains neutrophil supply during life-threatening infection in early life. Elevated levels of a vascular glycoprotein support emergency granulopoiesis in neonates by maintaining myeloid progenitor reserves, thereby preventing neutropenia and reducing mortality in experimental sepsis. This axis is modulated by anti- and pro-inflammatory cytokines, with one cytokine up-regulating the glycoprotein to enhance neutrophil output, while another cytokine exerts the opposite effect. Administration of the glycoprotein in deficient models restores neutrophil counts, curbs bacteremia and improves survival, highlighting a potential adjunctive therapy to bolster newborn defences against polymicrobial sepsis.

Neutrophil Function and Immune Response in Neonatal Health publication trend

The graph below shows the total number of articles in neutrophil function and immune response in neonatal health across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil extracellular traps (NETs): Meshes of DNA and antimicrobial proteins expelled by activated neutrophils to ensnare pathogens.

Emergency granulopoiesis: Accelerated production of neutrophils in the bone marrow in response to infection or inflammation.

Neutropenia: Abnormally low concentration of circulating neutrophils, increasing infection risk.

Phagocytosis: Process by which neutrophils engulf and digest microbes and debris.

Disease tolerance: Host strategy that limits tissue damage without directly reducing pathogen burden.

References

1. An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life. Nature Communications (2024).
2. Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps. Frontiers in Immunology (2023).
3. Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis. Critical Care (2019).
4. Age-Appropriate Functions and Dysfunctions of the Neonatal Neutrophil. Frontiers in Pediatrics (2017).
5. Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate Outcome in Neonatal Bacterial Sepsis. Frontiers in Immunology (2018).