Intracellular Pseudomonas aeruginosa within the Airway Epithelium of Cystic Fibrosis Lung Tissues

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Abstract
Rationale: Pseudomonas aeruginosa is the major bacterial pathogen colonizing the airways of adult patients with cystic fibrosis (CF) and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evade the immune system and antibiotic therapy. Although the ability of P. aeruginosa to invade and survive within epithelial cells has been described in vitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. Objectives: To detect and characterize intracellular P. aeruginosa in CF airway epithelium from human lung explant tissues. Methods: We sampled lung explant tissues from patients with CF undergoing lung transplantation and non-CF lung donor control tissue. We analyzed lung tissue sections for the presence of intracellular P. aeruginosa using quantitative culture and microscopy, in parallel to histopathology and airway morphometry. Measurements and Main Results: P. aeruginosa was isolated from the lungs of seven patients with CF undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P. aeruginosa within airway epithelial cells in three of the seven patients analyzed at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. Conclusions: This is the first study describing the presence of intracellular P. aeruginosa in CF lung tissues. Although intracellular P. aeruginosa in airway epithelial cells is likely relatively rare, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.
Funding Information
  • Cystic Fibrosis Foundation Therapeutics (NGUYEN21I0)
  • Cystic Fibrosis Canada (559985)
  • Burroughs Wellcome Fund (1019967)
  • Institute of Infection and Immunity (148827)
  • Réseau de Recherche en Santé Respiratoire
  • Fonds de Recherche Québec Santé (332282)
  • Cystic Fibrosis Foundation Therapeutics (NGUYEN21I0)
  • Cystic Fibrosis Foundation Therapeutics (559985)
  • Cystic Fibrosis Foundation Therapeutics (1019967)
  • Cystic Fibrosis Foundation Therapeutics (148827)
  • Réseau de Recherche en Santé Respiratoire
  • Fonds de Recherche Québec Santé (332282)

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