title: The Staphyloccous aureus Eap protein activates expression of proinflammatory cytokines.
abstract: 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.
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Sophie
authors.initials: S
authors.lastname: Sierro
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Massey
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1