AI Article Synopsis
- Secondary lung infections caused by Staphylococcus aureus (SA) are common and can be deadly in people infected with the influenza A virus (IAV).
- The study found that IAV hampers the body's natural defense by blocking liquid secretion in the alveoli and promoting liquid absorption, which worsens the conditions for fighting off SA infections.
- Restoring the secretion of alveolar wall liquid (AWL) could offer a potential new treatment strategy to help manage lung injuries from SA infections in IAV-infected individuals.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541650 | PMC |
| http://dx.doi.org/10.1172/JCI163402 | DOI Listing |
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