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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541650/ https://www.ncbi.nlm.nih.gov/pubmed/37581936 http://dx.doi.org/10.1172/JCI163402 |
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author | Tang, Stephanie De Jesus, Ana Cassandra Chavez, Deebly Suthakaran, Sayahi Moore, Sarah K.L. Suthakaran, Keshon Homami, Sonya Rathnasinghe, Raveen May, Alison J. Schotsaert, Michael Britto, Clemente J. Bhattacharya, Jahar Hook, Jaime L. |
author_facet | Tang, Stephanie De Jesus, Ana Cassandra Chavez, Deebly Suthakaran, Sayahi Moore, Sarah K.L. Suthakaran, Keshon Homami, Sonya Rathnasinghe, Raveen May, Alison J. Schotsaert, Michael Britto, Clemente J. Bhattacharya, Jahar Hook, Jaime L. |
author_sort | Tang, Stephanie |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10541650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-105416502023-10-02 Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection Tang, Stephanie De Jesus, Ana Cassandra Chavez, Deebly Suthakaran, Sayahi Moore, Sarah K.L. Suthakaran, Keshon Homami, Sonya Rathnasinghe, Raveen May, Alison J. Schotsaert, Michael Britto, Clemente J. Bhattacharya, Jahar Hook, Jaime L. J Clin Invest Research Article 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. American Society for Clinical Investigation 2023-10-02 /pmc/articles/PMC10541650/ /pubmed/37581936 http://dx.doi.org/10.1172/JCI163402 Text en © 2023 Tang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Tang, Stephanie De Jesus, Ana Cassandra Chavez, Deebly Suthakaran, Sayahi Moore, Sarah K.L. Suthakaran, Keshon Homami, Sonya Rathnasinghe, Raveen May, Alison J. Schotsaert, Michael Britto, Clemente J. Bhattacharya, Jahar Hook, Jaime L. Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection |
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 | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541650/ https://www.ncbi.nlm.nih.gov/pubmed/37581936 http://dx.doi.org/10.1172/JCI163402 |
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