Files
Abstract
Cystic fibrosis (CF) is a primarily pulmonary disease characterized by impaired mucociliary clearance and chronic bacterial infections. Pseudomonas aeruginosa is the main CF pathogen responsible for large-scale neutrophil recruitment in the airways. When neutrophils fail to clear bacteria, P. aeruginosa-induced neutrophil extracellular traps (NETs) likely form, during which neutrophil granulocytes release granule components with decondensed neutrophil DNA from the ruptured membrane. We aimed to determine the contribution of P. aeruginosas flagellum-powered motility to NET formation, and the role of MyD88 signaling in this pathway. Motile wild-type P. aeruginosa triggered significantly more NET formation than its motility- and flagellum- deficient counterparts. Additionally, MyD88 signaling was not involved in triggering NETosis. We propose bacterial motility is the primary virulence determinant responsible for triggering NETosis through a mechanism involving cooperation of multiple, MyD88-independent bacterial recognition receptors acting synergistically. This work could lead to potential therapeutic targets for controlling NET formation in CF airways.