Deciphering how Cystic Fibrosis impairs macrophage led immunity against Aspergillus spores

Cystic fibrosis (CF) is the most common inherited life-limiting disease in North European people affecting over 10,000 people in the UK. Progressive lung damage caused by infection and inflammation is the major determinant of survival, median age of death is 29 years. Strikingly, 50% of CF patients are infected with the fungal pathogen Aspergillus fumigatus and its presence is associated with reduced lung function and increased hospitalisation. Yet despite this, we don't understand why CF patients are more susceptible to Aspergillus-mediated diseases and this has limited our ability to develop new therapies to combat disease in these individuals. We have found that an immune cell that is crucial for clearing spores in healthy people, called macrophages, are less able to kill spores and mediate excessive inflammation in CF. We hypothesize that this altered macrophage response to fungal spores is mainly caused by the altered nature of the lung airways in CF patients. This study will assess why macrophages responses to Aspergillus are altered in CF patients, and whether these can be reversed by altering the lung airway environment. Our overall aim is to identify promising targets for future inventions that improve the outcome of Aspergillus disease in people with CF.