Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill Staphylococcus aureus.

Kayla Fantone,Arthur Miller,Rachel Fricker,Arlene A Stecenko,Balázs Rada,Ruchi Yadav,Samantha L Tucker,Eryn E Bernardy,Joanna B Goldberg

doi:10.3390/pathogens10060703

Kayla Fantone, Arthur Miller + Show 7 more

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https://doi.org/10.3390/pathogens10060703

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Abstract

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. Staphylococcus aureus (S. aureus) 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 S. aureus, it remains largely unknown why PMNs fail to eliminate S. aureus in CF. The goal of this study was to observe how the CF airway environment affects S. aureus killing by PMNs. PMNs were isolated from the blood of healthy volunteers and CF patients. Clinical isolates of S. aureus 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 S. aureus tested in vitro. The extent of killing varied among strains. When PMNs were pretreated with supernatants of CF sputum, S. aureus killing was significantly inhibited suggesting that the CF airway environment compromises PMN antibacterial functions. CF blood PMNs were capable of killing S. aureus. Although bacterial killing was inhibited with CF sputum, PMN binding and phagocytosis of S. aureus was not diminished. The S. aureus-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 S. aureus by PMNs and provides a new in vitro experimental model to study this phenomenon and its mechanism.

Highlights

Cystic fibrosis (CF) airway disease is characterized by decreased mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation.Pulmonary disease is the leading cause of morbidity and mortality in CF patients, due to the progression of chronic respiratory infections and host inflammation [1]
polymorphonuclear neutrophil granulocytes (PMNs) isolated from the blood of healthy volunteers are exposed to pooled supernatants of sputum samples collected from CF patients to mimic the CF airway environment
We hypothesized that PMNs from healthy individuals are capable of killing S. aureus isolates from CF patients, but bacterial killing would be inhibited by the CF airway environment

Summary

Introduction

Cystic fibrosis (CF) airway disease is characterized by decreased mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation. Pulmonary disease is the leading cause of morbidity and mortality in CF patients, due to the progression of chronic respiratory infections and host inflammation [1]. Staphylococcus aureus (S. aureus) is the most prevalent infectious agent in the respiratory tract of CF patients [2]. According to the United States’ Cystic Fibrosis Foundation’s annual reports in 2018 and 2019, 70% of CF patients were infected with S. aureus, including 25% with methicillin-resistant S. aureus (MRSA). S. aureus is one of the earliest pathogens recovered in the airways of CF children; it persists throughout the life of CF patients, and over a decade ago, surpassed P. aeruginosa as the most common airway pathogen in CF [3,4,5].

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