Targeting Interleukin 17 during nontuberculous mycobacterial lung infection in cystic fibrosis

Cystic Fibrosis is recognized as a single-gene disorder that affects several organs with major complications observed in the lung. Recent therapeutic treatments (e.g. Trikafta) are improving the quality of life and the health status of CF patients. Despite these encouraging results, efforts are still required to further limit the exaggerated inflammatory response with the aim to ameliorate CF pulmonary status. Indeed, the sustained inflammatory response remains a central pathological feature of CF lung disease and represents an important therapeutic target to limit detrimental inflammation without compromising the host defense against CF pathogens, such as Mycobacterium abscessus. The Interleukin(IL)-17 mediated immune axis represents an immunological determinant in pulmonary defense and function.  Whether the targeting of related biological molecules may differently determine the outcomes of pathologic processes (M. abscessus lung infection) is still unknown. Here, through a multidisciplinary approach, this research proposal will determine the beneficial use of targeting IL-17 to limit the exaggerated inflammatory response, tissue destruction and lung disease progression during CF chronic respiratory infection, such as M. abscessus. Finally, the developed designed strategy and the potential results of our project will impact to pwCF at risk of chronic lung infection either in which ETI modulator therapy is still not sufficient to break CF cycle of inflammation and infection, or in which cannot receive current ETI modulator therapy.