Biphasic lung injury during Streptococcus pneumoniae infection in a murine model
A Prevotat1, C Rouyer1, P Gosset2
1Recherche translationnelle : relations hôte pathogènes, université de Lille, CHU de Lille, EA7366, 59000 Lille, France.
Objectives:
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced lung injury.
Methods:
Using an in vitro model with 16HBE cells and experimental in vivo murine model of acute lung injury, we analyzed the epithelial response to S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and permeability was assessed by transepithelial resistance (TER) measurement and organization and expression of junction proteins. Functional consequences were studied with an in vivo murine model measuring alveolar permeability, distal alveolar fluid clearance (DAFC), and the alveolar inflammatory response.
Results:
In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial resistance, which was associated with significant modifications in the organization of junction proteins assessed by immunofluorescence staining and expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient increase in alveolar permeability with an adequate increase in DAFC 6hours post infection. In a second phase, a permanent increased permeability was associated with a major decrease in DAFC.
Conclusion:
Overall, the epithelial response to S. pneumoniae followed a biphasic pattern with an initial reversible increase in permeability related to the alteration of tight and adherens junctions and a second phase associated with an epithelial injury with a major increase in permeability with a decreased DAFC reflecting an injured alveolar capillary barrier.
Insights
Streptococcus pneumoniae causes pneumonia by disrupting lung epithelial barriers. This study reveals a biphasic response, initially reversible, then leading to significant epithelial injury and impaired lung function.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Cell Biology
Background:
- Streptococcus pneumoniae is a primary cause of community-acquired pneumonia.
- Understanding the lung epithelial response to S. pneumoniae is crucial for treating pneumonia.
Purpose of the Study:
- To analyze the epithelial response to Streptococcus pneumoniae-induced lung injury.
- To investigate the impact of S. pneumoniae on lung epithelial barrier function.
Main Methods:
- Utilized an in vitro model with 16HBE cells and an in vivo murine model of acute lung injury.
- Assessed epithelial permeability using transepithelial resistance (TER) and junction protein analysis.
- Measured alveolar permeability, distal alveolar fluid clearance (DAFC), and inflammatory response in vivo.
Main Results:
- In vitro, S. pneumoniae decreased TER and altered junction proteins.
- In vivo, S. pneumoniae caused a transient increase in alveolar permeability and DAFC, followed by a persistent increase in permeability and decreased DAFC.
- The epithelial response exhibited a biphasic pattern.
Conclusions:
- The epithelial response to S. pneumoniae is biphasic, involving reversible junction alteration and subsequent epithelial injury.
- Impaired alveolar-capillary barrier function, indicated by decreased DAFC, reflects severe epithelial injury.
- Findings highlight the critical role of epithelial barrier integrity in S. pneumoniae pneumonia.
