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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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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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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DOI: https://doi.org/10.1038/nm728