Extracellular vesicles secreted by primary human bronchial epithelial cells reduce Pseudomonas aeruginosa burden and inflammation in cystic fibrosis mouse lung
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 (...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 326; no. 2; pp. L164 - L174 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Physiological Society
01.02.2024
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1040-0605 1522-1504 1522-1504 |
DOI: | 10.1152/ajplung.00253.2023 |