Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection
Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-10-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI163402 |
| _version_ | 1797634424199708672 |
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| author | Stephanie Tang Ana Cassandra De Jesus Deebly Chavez Sayahi Suthakaran Sarah K.L. Moore Keshon Suthakaran Sonya Homami Raveen Rathnasinghe Alison J. May Michael Schotsaert Clemente J. Britto Jahar Bhattacharya Jaime L. Hook |
| author_facet | Stephanie Tang Ana Cassandra De Jesus Deebly Chavez Sayahi Suthakaran Sarah K.L. Moore Keshon Suthakaran Sonya Homami Raveen Rathnasinghe Alison J. May Michael Schotsaert Clemente J. Britto Jahar Bhattacharya Jaime L. Hook |
| author_sort | Stephanie Tang |
| collection | DOAJ |
| description | Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled SA. Loss of AWL secretion resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in the alveolar epithelium, and airspace liquid absorption was caused by stimulation of the alveolar epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization of inhaled SA, but rescue of AWL secretion protected against alveolar SA stabilization and fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled SA and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection. |
| first_indexed | 2024-03-11T12:07:28Z |
| format | Article |
| id | doaj.art-4566af0911ed4a1eb0dce8064a5f108a |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:28Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-4566af0911ed4a1eb0dce8064a5f108a2023-11-07T16:20:55ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-10-0113319Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfectionStephanie TangAna Cassandra De JesusDeebly ChavezSayahi SuthakaranSarah K.L. MooreKeshon SuthakaranSonya HomamiRaveen RathnasingheAlison J. MayMichael SchotsaertClemente J. BrittoJahar BhattacharyaJaime L. HookSecondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled SA. Loss of AWL secretion resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in the alveolar epithelium, and airspace liquid absorption was caused by stimulation of the alveolar epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization of inhaled SA, but rescue of AWL secretion protected against alveolar SA stabilization and fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled SA and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection.https://doi.org/10.1172/JCI163402Pulmonology |
| spellingShingle | Stephanie Tang Ana Cassandra De Jesus Deebly Chavez Sayahi Suthakaran Sarah K.L. Moore Keshon Suthakaran Sonya Homami Raveen Rathnasinghe Alison J. May Michael Schotsaert Clemente J. Britto Jahar Bhattacharya Jaime L. Hook Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection The Journal of Clinical Investigation Pulmonology |
| title | Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
| title_full | Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
| title_fullStr | Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
| title_full_unstemmed | Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
| title_short | Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
| title_sort | rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza staphylococcal coinfection |
| topic | Pulmonology |
| url | https://doi.org/10.1172/JCI163402 |
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