title: Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice.
abstract: 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.
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Meaghan
authors.initials: M
authors.lastname: FitzPatrick
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, AUSTRALIA.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Shenna
authors.initials: S
authors.lastname: Langenbach
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McQualter
authors.affiliation: 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.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.affiliation: The University of Melbourne, Department of Microbiology and Immunology, at The Peter Doherty Institute for Infection and Immunity, Melbourne, AUSTRALIA.
authors.forename: Odilia
authors.initials: O
authors.lastname: Wijburg
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Alastair
authors.initials: A
authors.lastname: Stewart
authors.affiliation: The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.|Department of Pharmacology, Monash University, Clayton, Victoria, AUSTRALIA.
authors.forename: Jane
authors.initials: J
authors.lastname: Bourke
authors.affiliation: RMIT University, School of Health Sciences and Health Innovations Research Institute, AUSTRALIA.|The University of Melbourne, Lung Health Research Centre, Department of Pharmacology &Therapeutics, Parkville, AUSTRALIA.
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
mesh_terms: D000403:Airway Resistance; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000473:pathology*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D060085:Coinfection / Q000150:complications; D005260:Female; D006651:Histocytochemistry; D009980:Influenza A virus / Q000254:growth & development*; D008168:Lung / Q000382:microbiology* / Q000473:pathology / Q000502:physiology*; D016210:Methacholine Chloride / Q000008:administration & dosage; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications*; D011008:Pneumococcal Infections / Q000150:complications*; D012129:Respiratory Function Tests; D013296:Streptococcus pneumoniae / Q000254:growth & development*
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride