Ricerc@Sapienza

Complex interplay between host immunity and pathogenic organisms has been proposed in Cystic fibrosis (CF) disease progression. Type I and III interferon (IFN) are involved in tuning antimicrobial and inflammation response as well as emerging negative modifier of respiratory infections. The use of IFN therapies or targeting the IFN pathway has been pursued in other diseases, but the IFN expression profiling in CF patients accordingly to the clinical and microbiological status is less well understood. The following aims will be pursued: i) to characterize viral and bacterial infections in CF mild or severe disease; to uncover the role of rhinovirus (HRV) species, viral load, genotype specific persistence; to assess airway type I/III IFN signature, according to bacterial/viral infections and patient data. We will collect about 1800 samples from the respiratory tract of patients. Respiratory samples will be analyzed for common and emerging microorganisms. Besides the bacteriological analysis, detection and typing of respiratory viruses will be performed. Gene expression evaluation of type I ¿III IFN profiling will be evaluated in CF patients accordingly to the bacteriological, virological and clinical data. The following output will be obtained: i) To delineate the presence and demonstrate the clinical value of the type I and III IFN-signature in CF disease; ii) To better understand the dynamics between bacteria and respiratory viruses in CF patients; iii) To ascertain whether virus¿bacteria coinfection compromise the IFN response. An improved understanding of the positive and/or negative effects of IFN response will enable clinicians and public health officials to identify which CF patients are at risk of developing this potentially fatal complication, and aid in the development of new therapeutic immunological approaches aimed at mitigating the severity of CF.