The role of neonatal neutrophil cells (NNC) for maturation of airway immunity and lung inflammation in neonates

• Applicant: Professorin Dr. Natascha Köstlin-Gille
• Subject Area: Pediatric and Adolescent Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575589276

Preterm birth is the main cause of perinatal morbidity and mortality. Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease and one of the most frequent complications in preterm infants and strongly associated with impaired neurodevelopmental outcome, reduced pulmonary function and increased risk for asthma-development in later life. Strategies to prevent BPD are limited and include avoidance of mechanical ventilation, application of caffeine and corticosteroids. The early postnatal period is considered as "window of opportunity" for priming lifelong health. Immediately after birth, the body surfaces get colonized by millions of bacteria, the so-called microbiome. This and other environmental factors drive immune and tissue maturation and influence the susceptibility to acute diseases during the neonatal period as well as chronic diseases in later life. Similar to the intestinal mucosa, the lung harbors highly differentiated immune cells regulating airway inflammation. It has been shown that dysregulation of airway immunity during early life leads to long-term impairment in respiratory health. Neutrophils are the first-line circulating effector immune cells responding to inflammation. However, there are significant differences in neutrophil immune responses between adults and neonates. Neonatal neutrophils exhibit various functional deficits compared to adult neutrophils, such as reduced chemotaxis, adhesion and transmigration as well as diminished production of antimicrobial proteins and reduced phagocytosis. For some time, the picture of neonatal neutrophils has changed and expanded once again. Newborns have high numbers of neutrophilic cells with immune-suppressive characteristics, the so-called granulocytic myeloid-derived suppressor cells (GR-MDSC), which expand under various pathological conditions usually leading to harmful immunosuppression especially by targeting T-cells but also mediate immune tolerance between mother and fetus during pregnancy. Thus, neutrophils in the newborn (here named as neonatal neutrophil cells, NNC) represent a heterogenous mixture of proinflammatory and suppressive immune cells. The role of NNC and especially GR-MDSC for regulation of neonatal airway immunity and for the pathogenesis of BPD has hardly been investigated yet. In this project we aim to investigate the hypotheses that (1) the biological properties of lung NNC change after birth away from tolerogenic, immunosuppressive properties towards proinflammatory properties (2) the damaging influences in the context of BPD lead to a more rapid change in the biological properties of NNC (3) GR-MDSC and their exosomes protect from early lung inflammation during BPD and (4) Preservation of the anti-inflammatory properties of NNC in the lungs has a protective effect on the development of BPD. Based on the results of this study, new approaches for the prevention of chronic lung diseases in newborns and later in life could be developed.

• DFG Programme: Research Grants