This Article Full Text (PDF) Other Versions of this Article: IAI.01699-07v1 76/5/2164    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Scriba, T. J. Articles by Massey, R. C. Search for Related Content PubMed PubMed Citation Articles by Scriba, T. J. Articles by Massey, R. C.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.01699-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The S. aureus Eap protein activates expression of proinflammatory cytokines

Nuffield Dept. of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK; University of Texas School of Public Health, 1200 Herman Pressler, Houston, TX 77030, USA; Dept. of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK; Dept. of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, UK

^* To whom correspondence should be addressed. Email: r.c.massey{at}bath.ac.uk.

	Abstract

The Eap protein secreted by the major human pathogen Staphylococcus aureus is known to have several effects on human immunity. We have recently added to these roles by demonstrating that Eap enhances interactions between MHC molecules and human leukocytes. Several studies have indicated that Eap can induce cytokine production by human peripheral blood mononuclear cells (PBMC). 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 IL-6 and TNF 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-ICAM-1 (CD54) antibodies inhibited this induction and implicated a role for this known Eap binding protein in cellular activation. IL-6 and TNF secretion was also observed by murine cells exposed to Eap. 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.