Abstract
A majority of the morbidity and mortality associated with the genetic disease Cystic Fibrosis (CF) is due to lung disease resulting from chronic respiratory infections. The CF airways become chronically colonized with bacteria in childhood, and over time commensal lung microbes are displaced by bacterial pathogens, leading to a decrease in microbial diversity that correlates with declining patient health. Infection with the pathogen Pseudomonas aeruginosa is a major predictor of morbidity and mortality in CF, with CF individuals often becoming chronically colonized with P. aeruginosa in early adulthood and thereafter having an increased risk of hospitalization. Progression of CF respiratory disease is also influenced by infection with respiratory viruses. Children and adults with CF experience frequent respiratory viral infections with respiratory syncytial virus (RSV), rhinovirus, influenza, parainfluenza, and adenovirus, with RSV and influenza infection linked to the greatest decreases in lung function. Along with directly causing severe respiratory symptoms in CF populations, the impact of respiratory virus infections may be more far-reaching, indirectly promoting bacterial persistence and pathogenesis in the CF respiratory tract. Acquisition of P. aeruginosa in CF patients correlates with seasonal respiratory virus infections, and CF patients colonized with P. aeruginosa experience increased severe exacerbations and declines in lung function during respiratory viral co-infection. In light of such observations, efforts to better understand the impact of viral-bacterial co-infections in the CF airways have been a focus of clinical and basic research in recent years. This review summarizes what has been learned about the interactions between viruses and bacteria in the CF upper and lower respiratory tract and how co-infections impact the health of individuals with CF.
Highlights
A majority of the morbidity and mortality associated with the genetic disease Cystic Fibrosis (CF) is due to lung disease resulting from chronic respiratory infections
The CF airways become chronically colonized with bacteria in childhood, and over time commensal lung microbes are displaced by bacterial pathogens, leading to a decrease in microbial diversity that correlates with declining patient health
Acquisition of P. aeruginosa in CF patients correlates with seasonal respiratory virus infections, and CF patients colonized with P. aeruginosa experience increased severe exacerbations and declines in lung function during respiratory viral co-infection
Summary
Cystic fibrosis (CF) is a lethal genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene [1] that result in dysfunction of the CFTR anion channel [2]. Diminished ASL hydration and thick mucus at the airway epithelial surface leads to failure of mucociliary clearance in the CF respiratory tract due to collapse of airway cilia, thereby preventing ciliary beat that normally clears debris, and infectious agents from the lungs This allows microorganisms to repeatedly infect, eliciting robust inflammatory responses dominated by elevated proinflammatory cytokines, and continued accumulation of neutrophils in the CF airway [5]. The dysregulated conductance of bicarbonate anions by the CFTR channel in CF results in improper mucus formation and an altered ASL pH, which impacts the function of secreted antimicrobial peptides, disrupting a first line of defense against invading bacterial pathogens [7,8,9] Together, these deficiencies in CF respiratory tract physiology prevent efficient clearance of pathogens from the airways, allowing for the establishment of a robust community of microbes
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