Adilia Warris, Neil Vargesson & Neil Gow
This research project will investigate the antifungal immune response of Cystic Fibrosis (CF) immune cells. CF is the most common genetically inherited disease (1 in 2500) in western populations. CF is caused by a gene mutation resulting in a disability of cells to handle sodium and chloride properly. The lungs are mainly affected by this and the airways of CF patients contain mucus and secretions which are thicker than normal. Although survival of CF patients is improving, median age of death is < 30 years, and progressive lung disease is the main cause of death.
Almost 50% of CF patients will be infected with Aspergillus fumigatus, a fungus abundantly present in our environment, leading to an increased risk of hospital admission due to exacerbation of lung disease. It remains unclear why A. fumigatus is able to reside in the lungs of CF-patients and how it can cause progressive lung disease. Although the sticky mucus in the lungs of CF patients will entrap the inhaled Aspergillus conidia, it doesn’t explain the infections observed.
We hypothesize that CF immune cells are hindered in mounting a proper immune response to clear A. fumigatus from the lungs. We choose to use a CF zebrafish model fish line to study the interaction between CF immune cells and A. fumigatus.
The zebrafish model has proved to be an extremely useful tool to study the immunology of several other infectious diseases and has led to new developments in the treatment of certain infections. We expect to establish a CF zebrafish model in which we will able to study in detail how CF immune cells interact upon Aspergillus infection. Next, this model will help us to answer the question why CF patients are suffering from Aspergillus infections.