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Infection and Immunity, May 2008, p. 2164-2168, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01699-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Staphyloccous aureus Eap Protein Activates Expression of Proinflammatory Cytokines{triangledown}

Thomas J. Scriba,1 Sophie Sierro,1 Eric L. Brown,2 Rodney E. Phillips,1 Andrew K. Sewell,3 and Ruth C. Massey4*

Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom,1 University of Texas School of Public Health, 1200 Herman Pressler, Houston, Texas 77030,2 Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, United Kingdom,3 Department of Biology and Biochemistry, University of Bath, Claverton Down BA2 7AY, United Kingdom4

Received 20 December 2007/ Returned for modification 8 February 2008/ Accepted 26 February 2008

The extracellular adhesion protein (Eap) secreted by the major human pathogen Staphylococcus aureus is known to have several effects on human immunity. We have recently added to knowledge of these roles by demonstrating that Eap enhances interactions between major histocompatibility complex molecules and human leukocytes. Several studies have indicated that Eap can induce cytokine production by human peripheral blood mononuclear cells (PBMCs). To date, there has been no rigorous attempt to identify the breadth of cytokines produced by Eap stimulation or to identify the cell subsets that respond. Here, we demonstrate that Eap induces the secretion of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-{alpha}) by CD14+ leukocytes (monocytes and macrophages) within direct ex vivo PBMC populations (note that granulocytes are also CD14+ but are largely depleted from PBMC preparations). Anti-intercellular adhesion molecule 1 (CD54) antibodies inhibited this induction and implicated a role for this known Eap binding protein in cellular activation. IL-6 and TNF-{alpha} secretion by murine cells exposed to Eap was also observed. The activation of CD14+ cells by Eap suggests that it could play a significant role in both septic shock and fever, two of the major pathological features of S. aureus infections.

* Corresponding author. Mailing address: Department of Biology and Biochemistry, University of Bath, Claverton Down BA2 7AY, United Kingdom. Phone: 44-1225-386018. Fax: 44-1225-386779. E-mail: r.c.massey{at}bath.ac.uk

{triangledown} Published ahead of print on 10 March 2008.

Editor: J. L. Flynn

Infection and Immunity, May 2008, p. 2164-2168, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.01699-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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