Blood Neutrophils Are Reprogrammed in Bronchiectasis.

Area of Science:

• Immunology
• Pulmonology
• Microbiology

Background:

• Neutrophilic airway inflammation is central to bronchiectasis, yet neutrophil behavior in this condition remains poorly understood.
• Understanding neutrophil function is crucial for developing targeted therapies for bronchiectasis.

Purpose of the Study:

• To investigate the phenotype and function of blood neutrophils in patients with bronchiectasis during stable periods and exacerbations.
• To compare blood and airway neutrophil function in bronchiectasis.

Main Methods:

• Assessed blood neutrophil apoptosis, cell surface markers, degranulation, reactive oxygen species generation, phagocytosis, and Pseudomonas aeruginosa killing in healthy volunteers and patients with bronchiectasis (stable and exacerbation).
• Compared blood and airway neutrophil function in bronchiectasis.
• Included patients with community-acquired pneumonia for comparison during exacerbations.

Main Results:

• Stable bronchiectasis patients exhibited blood neutrophils with prolonged survival, delayed apoptosis, increased CD62L shedding, upregulated CD11b, increased myeloperoxidase release, and impaired phagocytosis and killing of P. aeruginosa.
• Airway neutrophils in bronchiectasis showed reduced bacterial phagocytosis and killing compared to autologous blood neutrophils.
• Neutrophil function was impaired during exacerbations in both bronchiectasis and pneumonia, improving after antibiotic treatment.

Conclusions:

• Peripheral blood neutrophils in stable bronchiectasis are reprogrammed, exhibiting prolonged survival.
• This altered neutrophil phenotype impairs their ability to phagocytose and kill bacteria, contributing to the chronic inflammatory cycle in bronchiectasis.