Neutrophil extracellular trap release driven by bacterial motility: Relevance to cystic fibrosis lung disease

Abstract

ABSTRACTNeutrophil extracellular trap (NET) formation represents a unique effector function of neutrophils (PMN). The mechanism of NET release in response to bacteria is largely unknown. We studied the process by which Pseudomonas aeruginosa, an opportunistic pathogen, interacts with primary PMNs, and found that flagellar swimming motility of the bacterium is essential for inducing NET extrusion. Cystic fibrosis (CF) lung disease is associated with P. aeruginosa infection and PMN-dominated inflammation. Although NETs are abundant in CF airways, the main factors triggering NET release in CF remain unclear. Our study implicates that motile P. aeruginosa is a strong NET-inducer in CF. In early stages of CF lung disease flagellated, motile isolates of P. aeruginosa are characteristic and their interactions with PMNs could lead to NET formation. In chronic CF, P. aeruginosa down-regulates its flagellum expression to avoid recognition by the immune system and forms biofilms. Flagellated bacteria, however, are released from biofilms and could interact with PMNs to form NETs. Although flagellated forms likely represent only a small fraction of the total P. aeruginosa load in chronic CF, NET release induced by them could have a significant impact on inflammation and lung function since flagellated forms trigger the most robust response of the immune system including PMNs.Overall, we speculate that NET formation driven by motile P. aeruginosa could be a novel, significant contributor to pathogenesis at both, early and late stages of CF lung disease.