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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SpA has a role in the pathogenesis of murine pneumonia because spa mutants are unable to establish pulmonary infection in a mouse model, and tnfr1-null mice are highly resistant to S. aureus pneumonia.
“SpA also has a role in the pathogenesis of murine pneumonia because spa mutants are unable to establish pulmonary infection in a mouse model, and tnfr1null mice, lacking the SpA receptor, are highly resistant to S. aureus pneumonia (18).”
From Staphylococcus aureus protein A mediates invasion across airway epithelial cells through activation of RhoA GTPase signaling and proteolytic activity (2011) · cites this paper as [18]
Cites
TNF-R1 Signaling: A Beautiful Pathway
Chen, G., & Goeddel, D. V. (2002) · Science · doi:10.1126/science.1071924 · Cited by 1,930 · see citing works
Signal transduction by tumor necrosis factor and its relatives.
Baud, V., & Karin, M. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02064-5 · Cited by 1,741 · see citing works
Exotoxins of Staphylococcus aureus
Dinges, M. M., Orwin, P. M., & Schlievert, P. M. (2000) · Clinical Microbiology Reviews · doi:10.1128/cmr.13.1.16-34.2000 · Cited by 1,571 · see citing works
Surface protein adhesins of Staphylococcus aureus
Foster, T. J., & Höök, M. (1998) · Trends in Microbiology · doi:10.1016/s0966-842x(98)01400-0 · Cited by 985 · see citing works
Exotoxins of Staphylococcus aureus
Dinges, M. M., Orwin, P. M., & Schlievert, P. M. (2000) · Clinical Microbiology Reviews · doi:10.1128/cmr.13.1.16 · Cited by 974 · see citing works
The emergence and evolution of methicillin-resistant Staphylococcus aureus
Hiramatsu, K., Cui, L., Kuroda, M., & Ito, T. (2001) · Trends in Microbiology · doi:10.1016/s0966-842x(01)02175-8 · Cited by 825 · see citing works
Graille, M., Stura, E. A., Corper, A. L., Sutton, B. J., Taussig, M., Charbonnier, J., & Silverman, G. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5399 · Cited by 517 · see citing works
Functional Analysis of the Domain Structure of Tumor Necrosis Factor-α Converting Enzyme
Reddy, P., Slack, J. L., Davis, R., Cerretti, D. P., Kozlosky, C. J., Blanton, R. A., Shows, D. M., Peschon, J. J., & Black, R. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14608 · Cited by 501 · see citing works
The TNF-receptor-associated factor family
Wajant, H., Henkler, F., & Scheurich, P. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(01)00160-7 · Cited by 353 · see citing works
Tumor necrosis factor receptor superfamily members and their ligands
Armitage, R. J. (1994) · Current Opinion in Immunology · doi:10.1016/0952-7915(94)90119-8 · Cited by 308 · see citing works
van Heeckeren, A. M., Walenga, R. W., Konstan, M. W., Bonfield, T. L., Davis, P. B., & Ferkol, T. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119828 · Cited by 262 · see citing works
Protein A is the von Willebrand factor binding protein on Staphylococcus aureus.
Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., Hartford, O. M., Foster, T. J., Peters, G., Kehrel, B. E., & Herrmann, M. (2000) · PubMed · doi:10.1182/blood.v96.6.2149 · Cited by 228 · see citing works
Goerke, C., Campana, S., Bayer, M. G., Döring, G., Botzenhart, K., & Wolz, C. (2000) · Infection and Immunity · doi:10.1128/iai.68.3.1304-1311.2000 · Cited by 209 · see citing works
Wang, J. E., Jørgensen, P. F., Almlöf, M., Thiemermann, C., Foster, S. J., Aasen, A. O., & Solberg, R. (2000) · Infection and Immunity · doi:10.1128/iai.68.7.3965-3970.2000 · Cited by 201 · see citing works
Nguyen, T. T., Ghebrehiwet, B., & Peerschke, E. I. B. (2000) · Infection and Immunity · doi:10.1128/iai.68.4.2061-2068.2000 · Cited by 195 · see citing works
Protein A is a virulence factor in Staphylococcus aureus arthritis and septic death
Palmqvist, N., Foster, T. J., Tarkowski, A., & Josefsson, E. (2002) · Microbial Pathogenesis · doi:10.1006/mpat.2002.0533 · Cited by 191 · see citing works
Surface-associated proteins of<i>Staphylococcus aureus:</i>Their possible roles in virulence
Foster, T. J., & McDevitt, D. (1994) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1994.tb06828.x · Cited by 186 · see citing works
Ratner, A. J., Bryan, R. A., Weber, A. J., Nguyen, S., Barnes, D., Pitt, A., Gelber, S. E., Cheung, A. L., & Prince, A. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007703200 · Cited by 169 · see citing works
Self-citationShedding of interleukin‐6 receptor and tumor necrosis factor α
Althoff, K., Reddy, P., Voltz, N., Rose‐John, S., & Müllberg, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01278.x · Cited by 162 · see citing works
Regulation of human airway epithelial cell IL-8 expression by MAP kinases
Li, J., Kartha, S., Iasvovskaia, S., Tan, A., Bhat, R. K., Manaligod, J. M., Page, K., Brasier, A. R., & Hershenson, M. B. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00060.2002 · Cited by 144 · see citing works
Rajan, S., Cacalano, G., Bryan, R. A., et al. (2000) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.23.3.4098 · Cited by 143 · see citing works
Herring, A. C., Lee, J., McDonald, R. A., Toews, G. B., & Huffnagle, G. B. (2002) · Infection and Immunity · doi:10.1128/iai.70.6.2959-2964.2002 · Cited by 140 · see citing works
Heyer, G. L., Saba, S., Adamo, R., et al. (2002) · Infection and Immunity · doi:10.1128/iai.70.1.127-133.2002 · Cited by 110 · see citing works
Palma, M., & Cheung, A. L. (2001) · Infection and Immunity · doi:10.1128/iai.69.12.7858-7865.2001 · Cited by 108 · see citing works
Self-citationRegulation of Airway Epithelial Cell NF-κB-Dependent Gene Expression by Protein Kinase Cδ
Page, K., Li, J., Zhou, L., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.11.5681 · Cited by 103 · see citing works
Soell, M., Diab, M., Archipoff, G., Beretz, A., Herbelin, C. J., Poutrel, B., & Klein, J. P. (1995) · Infection and Immunity · doi:10.1128/iai.63.4.1380-1386.1995 · Cited by 101 · see citing works
Jung, Y. D., Fan, F., McConkey, D. J., Jean, M. E., Liu, W., Reinmuth, N., Stoeltzing, O., Ahmad, S. A., Parikh, A. A., Mukaida, N., et al. (2002) · Cytokine · doi:10.1006/cyto.2002.1034 · Cited by 98 · see citing works
Hattar, K., Fink, L., Fietzner, K., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.10.6287 · Cited by 34 · see citing works
TNF inhibitors: a review of the recent patent literature.
Watson, B. (2002) · PubMed · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
David, M. Z., & Daum, R. S. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00081-09 · Cited by 1,972 · see citing works
Howden, B. P., Davies, J. K., Johnson, P. D. R., Stinear, T. P., & Grayson, M. L. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00042-09 · Cited by 962 · see citing works
Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., & Missiakas, D. M. (2009) · The FASEB Journal · doi:10.1096/fj.09-135467 · Cited by 437 · see citing works
RetractedWardenburg, J. B., Patel, R. J., & Schneewind, O. (2007) · Infection and Immunity · doi:10.1128/iai.01313-06 · Cited by 348 · see citing works
Diep, B. A., Chan, L., Tattevin, P., Kajikawa, O., Martin, T. R., Basuino, L., Mai, T. T., Marbach, H., Braughton, K. R., Whitney, A. R., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912403107 · Cited by 347 · see citing works
Host defense and pathogenesis in Staphylococcus aureus infections
DeLeo, F. R., Diep, B. A., & Otto, M. (2009) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2008.10.003 · Cited by 269 · see citing works
“Protein A also has a more specific role in the pathogenesis of airway infections by interacting with the tumor necrosis factor a receptor on airway epithelia.(76)”
BackgroundStaphylococcus aureus Protein A Activates TNFR1 Signaling through Conserved IgG Binding Domains
Gómez, M. I., O'Seaghdha, M., Magargee, M., Foster, T. J., & Prince, A. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601956200 · Cited by 155 · see citing works
Self-citationMyles, I. A., Castillo, C. R., Barbian, K. D., Kanakabandi, K., Virtaneva, K., Fitzmeyer, E., Paneru, M., Otaizo-Carrasquero, F., Myers, T. G., Markowitz, T. E., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz8631 · Cited by 139 · see citing works
Staphylococcus aureus protein A activates TACE through EGFR‐dependent signaling
Gómez, M. I., Seaghdha, M. O., & Prince, A. S. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601554 · Cited by 108 · see citing works
Self-citationTLR2-induced calpain cleavage of epithelial junctional proteins facilitates leukocyte transmigration
Chun, J., & Prince, A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2008.11.009 · Cited by 87 · see citing works
Self-citationSoong, G., Chun, J., Parker, D., & Prince, A. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis244 · Cited by 84 · see citing works
Self-citationSoong, G., Martin, F. J., Chun, J., Cohen, T. S., Ahn, D. S., & Prince, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295386 · Cited by 73 · see citing works
Self-citationKim, G.-L., Hooven, T. A., Norambuena, J., Li, B., Boyd, J. M., Yang, J. H., & Parker, D. (2021) · mBio · doi:10.1128/mbio.00814-21 · Cited by 38 · see citing works
- Authors
- Gómez, M. I., Lee, A., Reddy, B., Muir, A., Soong, G., Pitt, A., Cheung, A., & Prince, A.
- Affiliations
- Columbia University (US)
- Dartmouth College (US)
- Corresponding author
- Prince, Alice
- Venue
- Nature Medicine
- Published
- 2004-07-11
- Volume
- 10
- Issue
- 8
- Pages
- 842-848
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1988700176
- Cited by
- 412
- References
- 29
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 12 · 2023: 19 · 2022: 12 · 2021: 15 · 2020: 12 · 2019: 17 · 2018: 15 · 2017: 19 · 2016: 23 · 2015: 17 · 2014: 23 · 2013: 15 · 2012: 24
- FWCI
- 15.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL079395)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Staphylococcus aureus, protein A, TNFR1, airway epithelium, inflammation, staphylococcal pneumonia, virulence factors, receptor signaling, polymorphonuclear leukocytes
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, Lung, Mice, Inbred C57BL, Neutrophils, Pneumonia, Staphylococcal, Staphylococcal Protein A, Staphylococcus aureus, Blotting, Western, Signal Transduction, Interleukin-8, Receptors, Tumor Necrosis Factor, Microscopy, Confocal, Respiratory Mucosa, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review