Abstract
Cystic fibrosis (CF) affects 70,000 patients worldwide. Morbidity and mortality in CF is largely caused by lung complications due to the triad of impaired mucociliary clearance, microbial infections and chronic inflammation. Cystic fibrosis airway inflammation is mediated by robust infiltration of polymorphonuclear neutrophil granulocytes (PMNs, neutrophils). Neutrophils are not capable of clearing lung infections and contribute to tissue damage by releasing their dangerous cargo. Pseudomonas aeruginosa is an opportunistic pathogen causing infections in immunocompromised individuals. P. aeruginosa is a main respiratory pathogen in CF infecting most patients. Although PMNs are key to attack and clear P. aeruginosa in immunocompetent individuals, PMNs fail to do so in CF. Understanding why neutrophils cannot clear P. aeruginosa in CF is essential to design novel therapies. This review provides an overview of the antimicrobial mechanisms by which PMNs attack and eliminate P. aeruginosa. It also summarizes current advances in our understanding of why PMNs are incapable of clearing P. aeruginosa and how this bacterium adapts to and resists PMN-mediated killing in the airways of CF patients chronically infected with P. aeruginosa.
Highlights
Cystic fibrosis (CF) affects 70,000 patients worldwide
This review provides an overview of the antimicrobial mechanisms by which polymorphonuclear neutrophil granulocytes (PMNs) attack and eliminate P. aeruginosa
These data obtained from clinical samples of cystic fibrosis (CF) patients clearly show that PMNs are the clinically most important leukocyte in CF airways, and PMN-mediated inflammation contributes to lung disease
Summary
Pseudomonas aeruginosa has a widespread occurrence in aqueous environments in nature [1,2] This ubiquitous, Gram-negative pathogen has a large genome that enables its adaptation to diverse growth conditions and infections in many species, ranging from nematodes to vertebrates, including humans [3,4]. Pathogens 2017, 6, 10 care-associated pneumonia) [11,12,13,14] This is due to the high prevalence of immunocompromised patients, biofilm growth of P. aeruginosa on plastic surfaces of medical devices, increased occurrence of multidrug-resistant strains in hospital wards and healthcare personnel carrying this bacterium [15,16,17,18]. P. aeruginosa infects the lungs of human patients with a variety of conditions, the disease most tightly associated with this bacterium is CF
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