LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation.
Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009375 |
| _version_ | 1819141448447033344 |
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| author | Lisa C Hennemann Shantelle L LaFayette Julien K Malet Perrine Bortolotti Tianxiao Yang Geoffrey A McKay Daniel Houle Danuta Radzioch Simon Rousseau Dao Nguyen |
| author_facet | Lisa C Hennemann Shantelle L LaFayette Julien K Malet Perrine Bortolotti Tianxiao Yang Geoffrey A McKay Daniel Houle Danuta Radzioch Simon Rousseau Dao Nguyen |
| author_sort | Lisa C Hennemann |
| collection | DOAJ |
| description | Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants. |
| first_indexed | 2024-12-22T11:54:37Z |
| format | Article |
| id | doaj.art-bf90d258e3c04ab581f8f7448141615d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T11:54:37Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-bf90d258e3c04ab581f8f7448141615d2022-12-21T18:26:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-03-01173e100937510.1371/journal.ppat.1009375LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation.Lisa C HennemannShantelle L LaFayetteJulien K MaletPerrine BortolottiTianxiao YangGeoffrey A McKayDaniel HouleDanuta RadziochSimon RousseauDao NguyenPseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.https://doi.org/10.1371/journal.ppat.1009375 |
| spellingShingle | Lisa C Hennemann Shantelle L LaFayette Julien K Malet Perrine Bortolotti Tianxiao Yang Geoffrey A McKay Daniel Houle Danuta Radzioch Simon Rousseau Dao Nguyen LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. PLoS Pathogens |
| title | LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. |
| title_full | LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. |
| title_fullStr | LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. |
| title_full_unstemmed | LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. |
| title_short | LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation. |
| title_sort | lasr deficient pseudomonas aeruginosa variants increase airway epithelial micam 1 expression and enhance neutrophilic lung inflammation |
| url | https://doi.org/10.1371/journal.ppat.1009375 |
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