Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1.
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.
Gómez
Marisa I
MI
Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
Lee
Aram
A
Reddy
Bharat
B
Muir
Amanda
A
Soong
Grace
G
Pitt
Allyson
A
Cheung
Ambrose
A
Prince
Alice
A
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000378:metabolism / Q000503:physiopathology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013205:Staphylococcal Protein A / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity
D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D013205:Staphylococcal Protein A