Aspergillus colonization and antifungal immunity in cystic fibrosis patients

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is the most common inherited life-limiting disease in North European people affecting 90,000 people worldwide. Progressive lung damage caused by recurrent infection and chronic airway inflammation is the major determinant of survival with a median age at death of 29 years. Approximately 60% of CF patients are infected with Aspergillus fumigatus, a ubiquitous environmental fungus, and its presence has been associated with accelerated lung function decline. Half of the patients infected with Aspergillus are <18 years of age. Yet time of acquisition of this fungus and determinants of CF-related Aspergillus disease severity and progression are not known. CFTR expression has been demonstrated in cells of the innate and adaptive immune system and has shown to be critical for normal function. Research delineating the role of CFTR-deficient phagocytes in Aspergillus persistence and infection in the CF lung, has only recently received attention. In this concise review we aim to present the current understanding with respect to when people with CF acquire infection with A. fumigatus and antifungal immune responses by CF immune cells.