Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks
Defective hydration of airway surface mucosa is associated with recurrent lung infection in cystic fibrosis (CF), a disease caused by CF transmembrane conductance regulator (<i>CFTR</i>) gene mutations. Whether the composition and/or presence of an airway surface liquid (ASL) is sufficie...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1587 |
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| author | Juliette L. Simonin Alexandre Luscher Davide Losa Mehdi Badaoui Christian van Delden Thilo Köhler Marc Chanson |
| author_facet | Juliette L. Simonin Alexandre Luscher Davide Losa Mehdi Badaoui Christian van Delden Thilo Köhler Marc Chanson |
| author_sort | Juliette L. Simonin |
| collection | DOAJ |
| description | Defective hydration of airway surface mucosa is associated with recurrent lung infection in cystic fibrosis (CF), a disease caused by CF transmembrane conductance regulator (<i>CFTR</i>) gene mutations. Whether the composition and/or presence of an airway surface liquid (ASL) is sufficient to prevent infection remains unclear. The susceptibility to infection of polarized wild type and <i>CFTR</i> knockdown (CFTR-KD) airway epithelial cells was determined in the presence or absence of a healthy ASL or physiological saline. CFTR-KD epithelia exhibited strong ASL volume reduction, enhanced susceptibility to infection, and reduced junctional integrity. Interestingly, the presence of an apical physiological saline alleviated disruption of the airway epithelial barrier by stimulating essential junctional protein expression. Thus, rehydrated CFTR-KD cells were protected from infection despite normally intense bacterial growth. This study indicates that an epithelial integrity gatekeeper is modulated by the presence of an apical liquid volume, irrespective of the liquid’s composition and of expression of a functional CFTR. |
| first_indexed | 2024-03-10T04:16:17Z |
| format | Article |
| id | doaj.art-ad456b46bfe549c5a4c25f0b2ab82762 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:16:17Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ad456b46bfe549c5a4c25f0b2ab827622023-11-23T08:01:28ZengMDPI AGCells2073-44092022-05-01119158710.3390/cells11091587Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional NetworksJuliette L. Simonin0Alexandre Luscher1Davide Losa2Mehdi Badaoui3Christian van Delden4Thilo Köhler5Marc Chanson6Department of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDefective hydration of airway surface mucosa is associated with recurrent lung infection in cystic fibrosis (CF), a disease caused by CF transmembrane conductance regulator (<i>CFTR</i>) gene mutations. Whether the composition and/or presence of an airway surface liquid (ASL) is sufficient to prevent infection remains unclear. The susceptibility to infection of polarized wild type and <i>CFTR</i> knockdown (CFTR-KD) airway epithelial cells was determined in the presence or absence of a healthy ASL or physiological saline. CFTR-KD epithelia exhibited strong ASL volume reduction, enhanced susceptibility to infection, and reduced junctional integrity. Interestingly, the presence of an apical physiological saline alleviated disruption of the airway epithelial barrier by stimulating essential junctional protein expression. Thus, rehydrated CFTR-KD cells were protected from infection despite normally intense bacterial growth. This study indicates that an epithelial integrity gatekeeper is modulated by the presence of an apical liquid volume, irrespective of the liquid’s composition and of expression of a functional CFTR.https://www.mdpi.com/2073-4409/11/9/1587mucosal immunity<i>P. aeruginosa</i>airway surface liquidepithelium integritycystic fibrosis |
| spellingShingle | Juliette L. Simonin Alexandre Luscher Davide Losa Mehdi Badaoui Christian van Delden Thilo Köhler Marc Chanson Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks Cells mucosal immunity <i>P. aeruginosa</i> airway surface liquid epithelium integrity cystic fibrosis |
| title | Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks |
| title_full | Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks |
| title_fullStr | Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks |
| title_full_unstemmed | Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks |
| title_short | Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks |
| title_sort | surface hydration protects cystic fibrosis airways from infection by restoring junctional networks |
| topic | mucosal immunity <i>P. aeruginosa</i> airway surface liquid epithelium integrity cystic fibrosis |
| url | https://www.mdpi.com/2073-4409/11/9/1587 |
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