Fig. 3

Several mechanisms require investigation concerning the dysfunctional innate immune response and NETs in Cystic Fibrosis (CF). It may be that CFTR ^−/− neutrophils are hyper-stimulatory to macrophages due to increased NET production and CFTR ^−/− alveolar macrophages produce higher levels of pro-inflammatory cytokines, driving chemotaxis of more neutrophils in a self-perpetuating cycle of inflammation. Co-culture experiments with airway epithelial cells, NETs and macrophages would mimic in vivo conditions. Targeting this cycle, e.g. by reducing NET production, inhibiting NET-protein’s deleterious functions or promoting NET clearance would provide new targets for the treatment of CF