Rada Balázs
College of Veterinary Medicine, Department of Infectious Diseases, The University of Georgia, 501 D.W. Brooks Drive, Athens, GA 30602, USA.
Pathogens. 2017 Mar 9;6(1):10. doi: 10.3390/pathogens6010010.
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.
囊性纤维化(CF)在全球影响着7万名患者。CF患者的发病率和死亡率主要由黏液纤毛清除功能受损、微生物感染和慢性炎症这三者导致的肺部并发症引起。囊性纤维化气道炎症是由多形核中性粒细胞(PMNs,即中性粒细胞)的大量浸润介导的。中性粒细胞无法清除肺部感染,并且通过释放其危险物质而导致组织损伤。铜绿假单胞菌是一种在免疫功能低下个体中引起感染的机会致病菌。铜绿假单胞菌是CF患者中的主要呼吸道病原体,感染大多数患者。虽然在免疫功能正常的个体中,中性粒细胞是攻击和清除铜绿假单胞菌的关键,但在CF患者中却无法做到。了解中性粒细胞在CF中为何无法清除铜绿假单胞菌对于设计新的治疗方法至关重要。本综述概述了中性粒细胞攻击和消除铜绿假单胞菌的抗菌机制。它还总结了目前我们在理解中性粒细胞为何无法清除铜绿假单胞菌以及这种细菌如何在长期感染铜绿假单胞菌的CF患者气道中适应并抵抗中性粒细胞介导的杀伤方面取得的进展。