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Sci Rep. 2016 Mar 4;6:22751. doi: 10.1038/srep22751.

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

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The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
Department of Pharmacology, Monash University, Clayton, Victoria, AUSTRALIA.
The WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at The Peter Doherty Institute for Infection and Immunity, Melbourne, AUSTRALIA.
The University of Melbourne, Department of Microbiology and Immunology, at The Peter Doherty Institute for Infection and Immunity, Melbourne, AUSTRALIA.
RMIT University, School of Health Sciences and Health Innovations Research Institute, AUSTRALIA.


There is emerging epidemiological data to suggest that upper respiratory tract bacterial colonisation in infancy may increase the risk of developing respiratory dysfunction later in life, and respiratory viruses are known to precipitate persistent colonisation. This study utilized a neonatal mouse model of Streptococcus pneumonia (SP) and influenza A virus (IAV) co-infection, where bronchoalveolar leukocyte infiltration had resolved by adulthood. Only co-infection resulted in persistent nasopharyngeal colonisation over 40 days and a significant increase in airway resistance in response to in vivo methacholine challenge. A significant increase in hysteresivity was also observed in IAV and co-infected mice, consistent with ventilatory heterogeneity and structural changes in the adult lung. Airway hyper-responsiveness was not associated with a detectable increase in goblet cell transdifferentiation, peribronchial smooth muscle bulk or collagen deposition in regions surrounding the airways. Increased reactivity was not observed in precision cut lung slices challenged with methacholine in vitro. Histologically, the airway epithelium appeared normal and expression of epithelial integrity markers (ZO-1, occludin-1 and E-cadherin) were not altered. In summary, neonatal co-infection led to persistent nasopharyngeal colonisation and increased airway responsiveness that was not associated with detectable smooth muscle or mucosal epithelial abnormalities, however increased hysteresivity may reflect ventilation heterogeneity.

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