Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice

Area of Science:

• Immunology
• Respiratory Medicine
• Microbiology

Background:

• Infant upper respiratory tract bacterial colonization may increase the risk of later-life respiratory dysfunction.
• Respiratory viruses can promote persistent bacterial colonization.

Purpose of the Study:

• To investigate the long-term effects of neonatal co-infection with Streptococcus pneumoniae (SP) and influenza A virus (IAV) on respiratory function in a mouse model.
• To determine if co-infection leads to persistent nasopharyngeal colonization and altered airway responsiveness in adulthood.

Main Methods:

• A neonatal mouse model was used to induce co-infection with SP and IAV.
• Airway resistance and responsiveness were assessed in adult mice using in vivo methacholine challenge.
• Hysteresivity, goblet cell transdifferentiation, smooth muscle bulk, collagen deposition, and epithelial integrity markers were evaluated.

Main Results:

• Only co-infection resulted in persistent nasopharyngeal colonization over 40 days.
• Co-infected mice exhibited significantly increased airway resistance and hysteresivity in response to methacholine.
• Increased airway responsiveness was not linked to smooth muscle or epithelial abnormalities, but hysteresivity suggested ventilatory heterogeneity.

Conclusions:

• Neonatal co-infection with SP and IAV establishes persistent nasopharyngeal colonization.
• This early-life infection leads to increased airway responsiveness and potential ventilatory heterogeneity in adult mice.
• The observed respiratory dysfunction was not associated with structural changes in airway smooth muscle or epithelium.