Extracellular vesicles secreted by primary human bronchial epithelial cells reduce Pseudomonas aeruginosa burden and inflammation in cystic fibrosis mouse lung

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 326; no. 2; pp. L164 - L174
• Main Authors: Sarkar, Sharanya, Barnaby, Roxanna, Nymon, Amanda B, Taatjes, Douglas J, Kelley, Thomas J, Stanton, Bruce A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2024
• Subjects: Adult; Amides; Animals; Antibiotic resistance; Antibiotics; Biofilms; Bronchopulmonary infection; Bronchus; Cystic fibrosis; Cystic Fibrosis - metabolism; Disease Models, Animal; Epithelial Cells; Epithelium; Extracellular vesicles; Extracellular Vesicles - metabolism; Humans; Immune response; Infections; Inflammation; Inflammation - metabolism; Lavage; Leukocytes (neutrophilic); Lung; Lungs; Mice; Morbidity; Neutrophils; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; Pseudomonas Infections; Respiratory function; Sensitivity enhancement; Trachea; Tumor necrosis factor-α; Vesicles; β-Lactam antibiotics; γ-Interferon; Pseudomonas aeruginosa; extracellular vesicles; cystic fibrosis; host-pathogen
• ISSN: 1040-0605; 1522-1504; 1522-1504
• DOI: 10.1152/ajplung.00253.2023

Cystic fibrosis (CF) results in a reduction in the volume of airway surface liquid, increased accumulation of viscous mucus, persistent antibiotic-resistant lung infections that cause chronic inflammation, and a decline in lung function. More than 50% of adults with CF are chronically colonized by ( ), the primary reason for morbidity and mortality in people with CF (pwCF). Although highly effective modulator therapy (HEMT) is an important part of disease management in CF, HEMT does not eliminate or lung inflammation. Thus, new treatments are required to reduce lung infection and inflammation in CF. In a previous in vitro study, we demonstrated that primary human bronchial epithelial cells (HBECs) secrete extracellular vesicles (EVs) that block the ability of to form biofilms by reducing the abundance of several proteins necessary for biofilm formation as well as enhancing the sensitivity of to β-lactam antibiotics. In this study, using a CF mouse model of infection, we demonstrate that intratracheal administration of EVs secreted by HBEC reduced lung burden and several proinflammatory cytokines including IFN-γ, TNF-α, and MIP-1β in bronchoalveolar lavage fluid (BALF), even in the absence of antibiotics. Moreover, EVs decreased neutrophils in BALF. Thus, EVs secreted by HBEC reduce the lung burden of , decrease inflammation, and reduce neutrophils in a CF mouse model. These results suggest that HBEC via the secretion of EVs may play an important role in the immune response to lung infection. Our findings show that extracellular vesicles secreted by primary human bronchial epithelial cells significantly reduce burden, inflammation, and weight loss in a cystic fibrosis mouse model of infection.