Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus

Area of Science:

• Pulmonary Medicine
• Immunology
• Neonatal Research

Background:

• Premature infants often need supplemental oxygen, impacting lung development and increasing susceptibility to respiratory infections.
• Neonatal hyperoxia is known to worsen adult lung responses to influenza A virus (IAV), causing inflammation, fibrosis, and mortality.

Purpose of the Study:

• To investigate how early-life hyperoxia influences the initial respiratory epithelium infection by IAV in a mouse model.
• To determine if neonatal hyperoxia alters the cellular response to IAV infection in adult mice.

Main Methods:

• Utilized a novel fluorescence-expressing reporter strain of H1N1 IAV (PR8-mCherry) in a neonatal hyperoxia mouse model.
• Employed whole lung imaging, histology, and flow cytometry to quantify viral expression and cellular infection.
• Analyzed the role of macrophages and epithelial cells in the host response to IAV.

Main Results:

• Neonatal hyperoxia increased morbidity and mortality in adult mice infected with IAV, similar to previous findings.
• Whole lung imaging showed a modest increase in viral expression, but flow cytometry revealed no significant increase in epithelial cell infection.
• A modest increase in viral expression was detected in CD45-positive macrophages, suggesting heightened macrophage activity.

Conclusions:

• Neonatal hyperoxia does not enhance early respiratory epithelial infection with IAV.
• Hyperoxia may increase macrophage activity against infected cells, contributing to enhanced early epithelial injury.
• Findings suggest a complex interplay between early-life oxygen exposure, viral infection, and immune cell responses in the lung.