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Intra-tracheal Administration of Haemophilus influenzae in Mouse Models to Study Airway Inflammation
Published on: March 2, 2016
Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus
Michael A O'Reilly1, Shauna H Marr, Min Yee
1Department of Pediatrics, Box 850, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. michael_oreilly@urmc.rochester.edu
Insights
Neonatal hyperoxia exposure in mice leads to increased lung inflammation and mortality when infected with influenza A virus as adults. This suggests early lung injury may permanently alter immune responses, worsening respiratory infections.
Area of Science:
- Pulmonary Medicine
- Immunology
- Developmental Biology
Background:
- Neonatal hyperoxia exposure in mice results in simplified lungs and reduced function, mimicking bronchopulmonary dysplasia (BPD) in humans.
- BPD survivors face a higher risk of respiratory infections, prompting investigation into hyperoxia's impact on influenza A virus infection response.
Purpose of the Study:
- To investigate if neonatal hyperoxia exacerbates influenza A virus infection severity in adult mice.
Main Methods:
- Adult female mice were exposed to room air or hyperoxia from postnatal days 1-4.
- Mice were subsequently infected with a sublethal dose of influenza A virus.
Main Results:
- Mice with neonatal hyperoxia showed significantly higher numbers of airway macrophages, neutrophils, and lymphocytes upon infection.
- Increased inflammation correlated with elevated monocyte chemotactic protein-1 (CCL2), while other cytokines and antibody responses were largely unchanged.
- Mortality increased by Day 14 post-infection in the hyperoxia group, linked to persistent inflammation and fibrosis.
Conclusions:
- Neonatal hyperoxia disrupts lung development and reprograms innate immune pathways in the lung.
- This reprogramming may contribute to the heightened pathology and reduced resistance to respiratory viral infections observed in individuals with a history of BPD.
Rationale:
Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection.
Objectives:
To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice.
Methods:
Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus.
Measurements And Main Results:
The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infection-associated changes in IFN-gamma, IL-1beta, IL-6, tumor necrosis factor-alpha, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1alpha, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis.
Conclusions:
These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.
