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Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection
Sungmin Moon1,2, Seunghan Han1,2, In-Hwan Jang3
1Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Abstract:
Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.
Insights
Influenza infection boosts Staphylococcus aureus attachment to airway cells by increasing CD47. Blocking this interaction improves survival, offering a potential therapy for secondary bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Respiratory viral infections heighten susceptibility to secondary bacterial infections.
- The specific mechanisms of airway epithelial involvement in bacterial superinfections are not fully understood.
Purpose of the Study:
- To investigate the role of CD47 in the airway epithelium during bacterial superinfection following viral infection.
- To identify the molecular interactions between airway epithelial cells and bacteria during superinfection.
Main Methods:
- Analyzing CD47 expression in human nasal and bronchial epithelial cells after influenza virus infection.
- Performing bacterial adhesion and in vitro pull-down assays to identify bacterial binding partners for CD47.
- Evaluating the impact of CD47 deficiency and antibody-mediated blockade on host survival in vivo.
Main Results:
- Influenza infection upregulated CD47 on the apical surface of ciliated airway epithelial cells.
- Staphylococcus aureus utilized CD47 as an attachment site via its fibronectin-binding proteins (FnBP), compromising epithelial barrier integrity.
- Ciliated cell-specific CD47 deficiency or antibody neutralization significantly improved host survival rates.
Conclusions:
- Airway epithelial CD47 plays a critical role in mediating Staphylococcus aureus superinfection after influenza.
- Targeting the CD47-fibronectin-binding protein interaction presents a potential therapeutic strategy to mitigate secondary bacterial infections.
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