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Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by
Elisabeth Schicke1,2, Zoltán Cseresnyés3, Knut Rennert4
1Institute of Medical Microbiology, Jena University Hospital, Am Klinikum1, D-07747 Jena, Germany.
Abstract:
Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia.
Insights
Bacterial infections, like Staphylococcus aureus, reduce lung surfactant protein-A (SP-A) levels. This decrease, influenced by immune cells, may worsen pneumonia outcomes.
Area of Science:
- Pulmonary immunology
- Infectious diseases
- Cellular biology
Background:
- Pneumonia is a leading cause of hospitalization globally.
- Bacterial co-infections, particularly with Staphylococcus aureus, worsen pneumonia severity.
- Surfactant protein-A (SP-A) is a key component of the lung's innate immune defense.
Purpose of the Study:
- To investigate the impact of influenza A virus (IAV) and Staphylococcus aureus (S. aureus) on SP-A expression.
- To elucidate the cellular mechanisms underlying SP-A regulation during infection.
- To validate findings in human alveolus-on-a-chip and murine pneumonia models.
Main Methods:
- Utilized a human alveolus-on-a-chip model to simulate lung microenvironment.
- Employed a murine pneumonia model for in vivo validation.
- Assessed SP-A expression and regulation in response to IAV and S. aureus infections.
- Investigated the role of TNF-α and macrophages in SP-A down-regulation.
Main Results:
- S. aureus reduces extracellular SP-A levels, potentially via bacterial proteases.
- SP-A expression is not directly affected by IAV or S. aureus in mono-epithelial cells.
- mRNA expression of SP-A is significantly down-regulated by TNF-α, induced by bacterial infection.
- Macrophage presence is crucial for SP-A down-regulation in the alveolus-on-a-chip model.
- S. aureus infection decreases SP-A levels in vivo in a murine pneumonia model.
Conclusions:
- Complex interactions between epithelial cells and immune cells, especially macrophages, lead to SP-A down-regulation.
- Bacterial infections, including mono- and super-infections, reduce SP-A expression in the lung.
- Reduced SP-A levels may contribute to the severity of bacterial pneumonia.
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