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Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1

Nature Medicine volume 10, pages 842–848 (2004)Cite this article

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-α (TNF-α) 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.

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Figure 1: Protein A induction of IL-8 in epithelial cells.
Figure 2: NF-κB and ATF-2 activation induced by protein A.
Figure 3: Recognition of protein A by TNFR1.
Figure 4: TNFR1 mobilization and shedding.
Figure 5: Protein A signaling through TNFR1.
Figure 6: Protein A induces inflammatory responses through TNFR1.

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Acknowledgements

Confocal microscopy was done at the Herbert Irving Optical Microscopy facility at Columbia University. This work was funded by the National Institutes of Health and the US Cystic Fibrosis Foundation. M.I.G. was a recipient of a postdoctoral fellowship from the US Cystic Fibrosis Foundation.

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Authors and Affiliations

  1. Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, 10032, New York, USA

    Marisa I Gómez, Aram Lee, Bharat Reddy, Amanda Muir, Grace Soong, Allyson Pitt & Alice Prince

  2. Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, 03755, New Hampshire, USA

    Ambrose Cheung

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  1. Marisa I Gómez
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Correspondence to Alice Prince.

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Gómez, M., Lee, A., Reddy, B. et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10, 842–848 (2004). https://doi.org/10.1038/nm1079

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