title: Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1.
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.
authors.affiliation: Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Marisa I
authors.initials: MI
authors.lastname: Gómez
authors.forename: Aram
authors.initials: A
authors.lastname: Lee
authors.forename: Bharat
authors.initials: B
authors.lastname: Reddy
authors.forename: Amanda
authors.initials: A
authors.lastname: Muir
authors.forename: Grace
authors.initials: G
authors.lastname: Soong
authors.forename: Allyson
authors.initials: A
authors.lastname: Pitt
authors.forename: Ambrose
authors.initials: A
authors.lastname: Cheung
authors.forename: Alice
authors.initials: A
authors.lastname: Prince
mesh_terms: 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
chemical_list: D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D013205:Staphylococcal Protein A