A major trust of this application is to explore how genetic variants of the prototypic long pentraxin PTX3 influence the susceptibility of cystic fibrosis patients to Pseudomonas aeruginosa and Aspergillus fumigatus infections. PTX3 is a non-redundant component of innate immunity against selected pathogens, including P. aeruginosa and A. fumigatus, microorganisms that play a key role in lung pathology of CF patients. Studies conducted in previous research projects funded by FFC demonstrated the therapeutic potential of PTX3 in the context of experimental chronic lung infections by P. aeruginosa. Now, the aim is to better define the role of genetic variants of PTX3 in influencing the susceptibility of CF patients to specific infections. It will be also evaluated whether CF is associated with a defect in the production of PTX3. This double approach possibly paves the way for identifying patients at higher risk of infection, and eventually candidate them for treatment with recombinant PTX3. These objectives will be pursued by means of genetic and functional studies with blood cells of healthy donors, preclinical studies in vitro and in vivo with the recombinant molecules and studies on blood samples of cystic fibrosis patients. We hypothesize that the information obtained through this study will accelerate the way for transferring to the patients this new anti-infective strategy.