Fantone Kayla, Tucker Samantha L, Miller Arthur, Yadav Ruchi, Bernardy Eryn E, Fricker Rachel, Stecenko Arlene A, Goldberg Joanna B, Rada Balázs
Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA.
Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Pathogens. 2021 Jun 4;10(6):703. doi: 10.3390/pathogens10060703.
Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill , it remains largely unknown why PMNs fail to eliminate in CF. The goal of this study was to observe how the CF airway environment affects killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of were obtained from the airways of CF patients. The results show that PMNs from healthy volunteers were able to kill all CF isolates and laboratory strains of tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing . Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of was not diminished. The -induced respiratory burst and neutrophil extracellular trap release from PMNs also remained uninhibited by CF sputum. In summary, our data demonstrate that the CF airway environment limits killing of by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.
囊性纤维化（CF）气道疾病的特征是慢性微生物感染和炎性多形核（PMN）粒细胞浸润。[具体病原体名称未给出]是CF中的主要肺部病原体，尽管存在PMN但仍持续存在，并与CF肺功能下降有关。虽然PMN是免疫系统杀死[具体病原体名称未给出]的主要机制，但在CF中PMN为何无法清除[具体病原体名称未给出]在很大程度上仍不清楚。本研究的目的是观察CF气道环境如何影响PMN对[具体病原体名称未给出]的杀伤作用。从健康志愿者和CF患者的血液中分离出PMN。[具体病原体名称未给出]的临床分离株取自CF患者的气道。结果表明，来自健康志愿者的PMN能够在体外杀死所有测试的CF分离株和[具体病原体名称未给出]的实验室菌株。杀伤程度因菌株而异。当PMN用CF痰液上清液预处理时，[具体病原体名称未给出]的杀伤作用明显受到抑制，这表明CF气道环境损害了PMN的抗菌功能。CF血液中的PMN能够杀死[具体病原体名称未给出]。尽管CF痰液抑制了细菌杀伤，但PMN对[具体病原体名称未给出]的结合和吞噬作用并未减弱。CF痰液也未抑制[具体病原体名称未给出]诱导的PMN呼吸爆发和中性粒细胞胞外陷阱释放。总之，我们的数据表明，CF气道环境限制了PMN对[具体病原体名称未给出]的杀伤作用，并提供了一个新的体外实验模型来研究这一现象及其机制。
