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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
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.
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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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