Asthma is a complex heterogenous disease, which may involve a dynamic interplay between multiple gene and environmental factors. There is a growing need to develop better therapies for the treatment and prevention of asthma. In order for this to occur an improved understanding of disease origins and pathogenesis is required. This thesis utilises experimental animal modelling and in vitro culture systems in order to dissect the pathways and mechanisms underlying the interaction between respiratory infections, the innate immune system, and asthma. This thesis consists of three publications. The first publication examines the role of immune evasion of Chlamydophila pneumoniae in its association with acute exacerbations of asthma, and how immune deviation of dendritic cells may be central to both outcomes. The second publication investigates the association between Respiratory Syncytial Virus (RSV) and asthma. This work defines a mechanism by which the innate immune system may induce a viral-specific Th2 response. The third publication attempts to delineate a possible 2-hit hypothesis of asthma pathogenesis. This involves mouse modelling of a specific genetic susceptibility (identified in humans) and an early-life viral infection acting as an environmental insult to the respiratory tract. This work evaluates whether an interplay between these two factors and the innate immune system could potentially predispose to the hallmark features of asthma in later-life.
University of Newcastle Research Higher Degree Thesis