Taken together we could show that P. aeruginosa is able to suppress the antiviral response of bronchial epithelial cells by the direct degradation of IFNλ. This degradation was dependent on the quorum sensing transcription factor LasR and the protease AprA. In addition, the infection status of CF patients was associated with the potential to degrade IFNλ and with presence of respiratory viruses in sputum. Therefore, we conclude that interfering with the antiviral response might lead to an increased susceptibility of P. aeruginosa infected CF patients for respiratory viruses causing respiratory exacerbations or foster the conversion of intermittent to chronic P. aeruginosa infections.