Epithelial-mesenchymal transition in paediatric airway epithelial cells following infection with bronchiolitis obliterans associated adenoviruses
Stephen Stick, Anthony Kicic, Christopher Blyth, Luke Garratt
Project description
Epithelial-mesenchymal transition (EMT) is a biological process involving the transition of airway epithelial cells (AEC) to a fibrotic phenotype and is a key process for fibrosis in bronchiolitis obliterans (BO). Post-infectious BO is a rare paediatric lung disease observed after particular viral infections, predominantly AV types 3, 5, 7 and 21 but also respiratory syncytial virus (RSV) and influenza, or infection by Mycoplasma pneumoniae.
Histologically, a mainly constrictive pattern of BO is observed, characterised by peribronchiolar fibrosis with lumen narrowing and variable degrees of inflammation and airway obliteration that are responsible for respiratory morbidity. Clinical evidence suggests that BO is immune mediated, with increased TNF-α, IL-1β and IL-8. However, there are few mechanistic studies on the lung parenchyma and no study has investigated the response of paediatric primary AEC to AV types 3, 5, 7 and 21. This gold-standard model could identify the causative mechanisms and furthermore, allow assessment of treatments to prevent EMT responses to AV. For example, azithromycin and other macrolides such as rapamycin have demonstrated efficacy in adults with BO but have not been studied in children, where treatment remains palliative.
Plain Language summary
Post-infectious bronchiolitis obliterans (PI-BO) is a rare lung disease. It can occur after a lung infection in childhood with particular types of virus called adenoviruses. This leads to scarring of the lung and affects breathing. Why PI-BO occurs following some but not all infections is not well understood and there are no known treatments. Our group has established in the laboratory a model of airway viral infection. We will use this model to answer whether lung cells behave differently after being exposed to adenoviruses that can cause PI-BO.
Funders of the project
Penn Medicine Orphan Disease Centre
Our Investigators
Anthony Kicic
BSc (Hons) PhD
Christopher Blyth
MBBS (Hons) DCH FRACP FRCPA PhD
Co-Director, Wesfarmers Centre of Vaccines and Infectious Diseases; Co-Head, Infectious Diseases Epidemiology, Wesfarmers Centre of Vaccines and Infectious Diseases, Honorary and NHMRC Career Development Fellow
Email me