Does viral infections cause the development of asthma? - Interactions between mast cells and the damaged epithelium

Important results from the project

The pathology of severe asthma has been little studied, especially in children. Alternative mediators driving the disease need to be sought for which will become an important field of research. Both the mast cell and the airway epithelium are key players in the inflammation observed in several asthma phenotypes. However, there is a great lack in information in how these two important cells interact. The overall purpose was to define mechanisms that may be applied to improve diagnosis and treatment of different phenotypes of asthma.

Expected long term effects

I have shown that children with asthma have a hyperresponsive epithelium, with increased secretion of inflammatory mediators. In asthmatic children, viral infections down regulate the ability of the epithelium to respond to damage. Furthermore, I have demonstrated that a viral infection affecting the peripheral lung evokes a rapid accumulation of mast cells in the alveolar parenchyma in children with respiratory infections. An expansion of mast cells early in life might therefore affect sensitization and susceptibility towards allergens and asthma development later in life.

Approach and implementation

Mast cells were characterized in bronchial biopsies and lung tissue from pediatric and adult patients with viral infections or asthma using immunohistochemistry. To study the effect of innate cytokines and viral infections in vitro models of epithelial cells from patients with different phenotypes of asthma was set up. The response towards these stimuli was studied using techniques of gene and protein expression. I used a unique live imaging technique (IncuCyte) that enabled me to study the behavior and wound healing response of epithelial cells towards different noxious stimuli.