For this study we specifically optimized the virulence of a bacteriophage of our collection towards this clinical strain and studied its efficacy both in vitro and in vivo. A clinical strain of P. aeruginosa isolated from a CF patient was used to evaluate bacteriophage curative and preventive treatments on a lung infection model. Both treatments successfully rescued mice from lethal infections, underlying the potential use of bacteriophages to combat lung pathogens. We also showed that pro-inflammatory and cytotoxicity markers, as well as histology observations, were all concordant with these results for survival. Moreover, we observed that bacterial debris released during bacteriophage treatments were not pro-inflammatory, as production of cytokines was not strongly stimulated in either the curative or the preventive treatments. A pro-inflammatory response is often used as an argument against phage therapy. Four days after administration of the preventative treatment that consisted of intranasal bacteriophage solution only, the lung concentrations of IL-6 and KC were low. The main cause of bacterial destruction can therefore be attributed to the bacteriophage itself. However, the cytokine concentrations were still significantly higher than those measured 24 h after administration of a PBS MK-1775 control solution, and partial involvement of a weak immune response stimulated by the bacteriophage solution cannot thus be ruled out. Indeed, the quality of the bacteriophage preparation, particularly the elimination of endotoxins, influenced the extent of the immune response following pre-infection treatments. This is in contrast to post-infection treatments, where the immune system has already been primed by bacteria when the bacteriophages were administered. Humans are constantly exposed to bacterial viruses an estimated 1031 are on the Earth —but little is known about the immunological consequences of this. Recently, a metagenomic analysis of viral DNA present in the lungs of CF patients identified over 100 different viral genomes, and this was considered to be a low diversity compared with other environments. Nevertheless, the role of the immune system in shaping viral diversity has yet to be deeply studied. Furthermore, the immune response to therapeutic bacteriophages has not been extensively investigated because most of the available data were obtained from model viruses which have little interest as therapeutic agents. Bacteriophage treatments of P. aeruginosa chronic lung infections in animal models have still not been investigated, and no specific procedure has been developed to isolate bacteriophages with higher infectivity against chronic clinical strains. However, several lines of evidence are encouraging. First, some bacteriophages are known to possess hydrolases that degrade bacterial exopolysaccharides. Second, several in vitro biofilm models have shown that bacteriophages can access and infect bacteria grown under these conditions.