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Updated: May 24, 2026
Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection
Published on: September 19, 2025
Lung development and the host response to influenza A virus are altered by different doses of neonatal oxygen in mice
Bradley W Buczynski1, Min Yee, B Paige Lawrence
1Department of Environmental Medicine, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Ave., Rochester, NY 14642, USA.
Insights
High oxygen exposure in preterm infants can harm lung development and increase infection risk. However, different oxygen levels disrupt lung development and viral infection responses, suggesting lung function alone may not predict future infection susceptibility.
Area of Science:
- Neonatal care
- Pulmonary medicine
- Infectious disease
Background:
- Neonatal oxygen exposure is linked to impaired lung development and heightened susceptibility to respiratory viral infections.
- Previous studies identified nonlinear thresholds for oxygen exposure affecting lung development: 40-60% for modest changes and 80-100% for severe changes.
Purpose of the Study:
- To determine if the identified oxygen exposure thresholds for altered lung development correlate with the severity of respiratory viral infection outcomes.
- To investigate the dose-dependent effects of neonatal oxygen exposure on the host response to viral infection in adult mice.
Main Methods:
- Mice were exposed to varying concentrations of oxygen (room air, 40%, 60%, 80%, 100%) during the first four postnatal days.
- Adult mice were subsequently infected with a respiratory virus to assess body weight loss, inflammation, and fibrosis.
- Monocyte chemoattractant protein-1 (MCP-1) levels were measured, and experiments using heterozygous Mcp-1 mice were conducted.
Main Results:
- Neonatal exposure to 100% and, to a lesser extent, 80% oxygen led to exacerbated weight loss, persistent inflammation, and fibrosis post-infection compared to room air controls.
- Exposure to 40% or 60% oxygen did not significantly alter the host response to infection.
- MCP-1 levels were elevated in infected mice exposed to 80% or 100% oxygen, but reducing MCP-1 did not mitigate oxygen-dependent infection responses.
Conclusions:
- Lung development and the host response to respiratory viral infection are differentially affected by oxygen dosage.
- The dose of oxygen that disrupts lung development may not be the same dose that increases susceptibility to viral infections.
- Assessing lung function alone may be insufficient to identify premature infants at risk for later respiratory viral infections.
Abstract:
Oxygen exposure in preterm infants has been associated with altered lung development and increased risk for respiratory viral infections later in life. Although the dose of oxygen sufficient to exert these changes in humans remains unknown, adult mice exposed to 100% oxygen between postnatal days 1-4 exhibit alveolar simplification and increased sensitivity to influenza virus infection. Additionally, two nonlinear thresholds of neonatal oxygen exposures were previously identified that promote modest (between 40% and 60% oxygen) and severe (between 80% and 100% oxygen) changes in lung development. Here, we investigate whether these two thresholds correlate with the severity of lung disease following respiratory viral infection. Adult mice exposed to 100% oxygen at birth, and to a lesser extent 80% oxygen, demonstrated enhanced body weight loss, persistent inflammation, and fibrosis following infection compared with infected siblings exposed to room air at birth. In contrast, the host response to infection was indistinguishable between mice exposed to room air and 40% or 60% oxygen. Interestingly, levels of monocyte chemoattractant protein (MCP)-1 were equivalently elevated in infected mice that had been exposed to 80% or 100% oxygen as neonates. However, reducing levels of MCP-1 using heterozygous Mcp-1 mice did not affect oxygen-dependent changes in the response to infection. Thus lung development and the host response to respiratory viral infection are disrupted by different doses of oxygen. Our findings suggest that measuring lung function alone may not be sufficient to identify individuals born prematurely who have increased risk for respiratory viral infection.