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Published on: December 15, 2014
Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1
Marisa I Gómez1, Aram Lee, Bharat Reddy
1Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Abstract:
Staphylococcus aureus is a major human pathogen that is associated with diverse types of local and systemic infection characterized by inflammation dominated by polymorphonuclear leukocytes. Staphylococci frequently cause pneumonia, and these clinical isolates often have increased expression of protein A, suggesting that this protein may have a role in virulence. Here we show that TNFR1, a receptor for tumor-necrosis factor-alpha (TNF-alpha) that is widely distributed on the airway epithelium, is a receptor for protein A. We also show that the protein A-TNFR1 signaling pathway has a central role in the pathogenesis of staphylococcal pneumonia.
Insights
Staphylococcus aureus pneumonia involves Protein A binding to the TNFR1 receptor on airway cells. This interaction is crucial for the development of staphylococcal pneumonia, highlighting a key virulence mechanism.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Staphylococcus aureus is a significant human pathogen causing various infections.
- Staphylococcal pneumonia is often associated with increased expression of Protein A, a key virulence factor.
- Inflammation in staphylococcal infections is characterized by polymorphonuclear leukocytes.
Purpose of the Study:
- To investigate the role of Protein A in Staphylococcus aureus virulence.
- To identify the specific receptor for Protein A on airway epithelial cells.
- To elucidate the signaling pathway involved in staphylococcal pneumonia pathogenesis.
Main Methods:
- Investigated the interaction between Protein A and tumor necrosis factor receptor 1 (TNFR1).
- Utilized airway epithelial cells expressing TNFR1.
- Analyzed the Protein A-TNFR1 signaling pathway in the context of pneumonia.
Main Results:
- Demonstrated that TNFR1, a receptor for tumor necrosis factor-alpha (TNF-alpha), is a direct receptor for Staphylococcus aureus Protein A.
- Showed that Protein A binds to TNFR1 on airway epithelial cells.
- Established the Protein A-TNFR1 signaling pathway as central to staphylococcal pneumonia pathogenesis.
Conclusions:
- Protein A utilizes the TNFR1 receptor on airway epithelium to mediate staphylococcal pneumonia.
- The Protein A-TNFR1 interaction represents a critical virulence mechanism for Staphylococcus aureus.
- Targeting this pathway could offer new therapeutic strategies against staphylococcal pneumonia.
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