chapter  12
18 Pages

In vitro models of bronchial epithelial cell infection

WithPeter AB Wark, Donna E Davies and Stephen T Holgate

The aim of in vitro models is to mimic the natural process of a disease in a framework that can be studied in depth and where the environment can be altered so as to investigate tissue responses. In terms of respiratory viral infections of humans, investigators are restricted in their ability to study the disease in vivo, particularly with respect to virus infection as a trigger of acute exacerbations of asthma. While this is a common cause of exacerbations in adults and children it is a challenging entity to study in terms of the inflammatory response of the airways from the time of initial infection, the subsequent immune response and the impact this has on asthma, both acutely and in the long term. Histological analysis of the lower airways is difficult and restricted to the proximal airways or by sampling airway secretions using induced sputum or bronchial lavage. The natural history of a virus-induced exacerbation of asthma is difficult to study, as this occurs several days after the initial virus infection and the pathological response is lost in the acute lower airway inflammation seen in acute asthma. For these reasons in vitro models have been developed to allow in-depth study of the mechanisms of epithelial cell infection and their response in terms of releasing proinflammatory mediators to recruit immune cells, wound repair and antiviral responses. Several respiratory viruses have

been associated with acute exacerbations of asthma, including human rhinoviruses (RVs), influenza viruses, respiratory syncytial virus (RSV), the parainfluenza viruses, coronaviruses and most recently human metapneumovirus. This chapter focuses on RVs and to a lesser extent RSV and influenza viruses, as these are the most common viruses associated with acute asthma and the viruses most extensively studied using in vitro models.