Network analysis reveals age- and virus-specific circuits in nasal epithelial cells of extremely premature infants.

BACKGROUND AND OBJECTIVES: Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. METHODS: Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. RESULTS: Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular-viral networks, emphasizing highly relevant virus-specific pathways, independent of viral replication kinetics. CONCLUSION: This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.

Regular lung recruitment maneuvers during high-frequency oscillatory ventilation in extremely preterm infants: a randomized controlled trial.

BACKGROUND: Lung recruitment maneuvers (LRMs) improve lung volume at initiation of high-frequency oscillatory ventilation (HFOV), but it is unclear when to repeat LRMs. We evaluated the efficiency of scheduled LRMs. METHODS: In a randomized controlled trial, extremely preterm infants on HFOV received either LRMs at 12-hour intervals and when clinically indicated (intervention) or only when clinically indicated (control). The primary outcome was the cumulative oxygen saturation index (OSI) over HFOV time, limited to 7 days. Additionally, LRMs were analyzed with respect to OSI improvement. RESULTS: Fifteen infants were included in each group. The mean (SD) postmenstrual age and weight at HFOV start were 23 + 6 (0 + 5) weeks and 650 (115) g in the intervention group and 24 + 4 (0 + 6) weeks (p = 0.03) and 615 (95) g (p = 0.38) in the control group. The mean (SD) cumulative OSI amounted to 4.95 (1.72) in the intervention versus 5.30 (2.08) in the control group (p = 0.61). The mean (SD) number of LRMs in 12 h was 1.3 (0.2) in the intervention versus 1.1 (0.5) in the control group (p = 0.13). Performing LRM when FiO2 > 0.6 resulted in a mean OSI reduction of 3.6. CONCLUSION: Regular versus clinically indicated LRMs were performed with equal frequency in preterm infants during HFOV, and consequently, no difference in lung volume was observed. LRMs seem to be most efficient at high FiO2. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04289324 (28/02/2020).

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL-29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL-29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG-ODN2216 in the presence or absence of IL-29 and assessed for IFN-α production, downstream-signaling, and activation marker expression. A significantly lower IL-29 production after TLR9-specific stimulation was demonstrated in neonatal pDCs. IL-29 enhanced the IFN-α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL-10 and IL-28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG-ODN2216/IL-29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL-29. Potential therapeutic agents enhancing the IL-29 response in neonatal pDCs possibly augment viral protection in newborns.