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Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes

Nature Medicine volume 8, pages 687–693 (2002)Cite this article

Abstract

Staphylococcus aureus is a human pathogen that secretes proteins that contribute to bacterial colonization. Here we describe the extracellular adherence protein (Eap) as a novel anti-inflammatory factor that inhibits host leukocyte recruitment. Due to its direct interactions with the host adhesive proteins intercellular adhesion molecule 1 (ICAM-1), fibrinogen or vitronectin, Eap disrupted β2-integrin and urokinase receptor–mediated leukocyte adhesion in vitro. Whereas Eap-expressing S. aureus induced a 2–3-fold lower neutrophil recruitment in bacterial peritonitis in mice as compared with an Eap-negative strain, isolated Eap prevented β2-integrin-dependent neutrophil recruitment in a mouse model of acute thioglycollate-induced peritonitis. Thus, the specific interactions with ICAM-1 and extracellular matrix proteins render Eap a potent anti-inflammatory factor, which may serve as a new therapeutic substance to block leukocyte extravasation in patients with hyperinflammatory pathologies.

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Figure 1: Influence of Eap on the adhesion of myelomonocytic U937 cells.
Figure 2: Interference of Eap with adhesion receptors of leukocytes.
Figure 3: Binding of Eap to different adhesion receptors and extracellular matrix proteins.
Figure 4: Contribution of Eap in the adhesion of S. aureus to ICAM-1.
Figure 5: Inhibition of neutrophil emigration by Eap in acute inflammation in vivo.

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Acknowledgements

We thank T. Schmidt-Wöll, S. Tannert-Otto and J. Weber for technical assistance; and G. Hoyer-Hansen, S. Bodary and D.B. Cines for reagents. This work was supported in part by grants from the Novartis Foundation for Therapeutical Research (to K.T.P. and T.C.), the Wilhelm–Sander Foundation (to K.T.P.) and by grants from the Deutsche Forschungsgemeinschaft (Specialized Research Centers 293 and 492 to M. Herrman and G.P.).

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Authors and Affiliations

  1. Institute for Biochemistry, Justus-Liebig-Universität, Giessen, Germany

    Triantafyllos Chavakis, Sandip M. Kanse & Klaus T. Preissner

  2. Third Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany

    Triantafyllos Chavakis & Reinhard G. Bretzel

  3. Institute of Medical Microbiology, University Hospital, Münster, Germany

    Muzaffar Hussain & Georg Peters

  4. Department of Microbiology, Pathology and Immunology, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden

    Jan-Ingmar Flock

  5. Department of Bacteriology and Hygiene, Institute of Medical Microbiology and Hygiene, Saarland University Hospital, Homburg/Saar, Germany

    Mathias Herrmann

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Correspondence to Triantafyllos Chavakis.

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Chavakis, T., Hussain, M., Kanse, S. et al. Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nat Med 8, 687–693 (2002). https://doi.org/10.1038/nm728

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