title: Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2.
abstract: Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland Education & Research Centre, Beaumont Hospital, Dublin, Ireland. nstevens@rcsi.ie
authors.forename: Niall T
authors.initials: NT
authors.lastname: Stevens
authors.forename: Irina
authors.initials: I
authors.lastname: Sadovskaya
authors.forename: Said
authors.initials: S
authors.lastname: Jabbouri
authors.forename: Tafiq
authors.initials: T
authors.lastname: Sattar
authors.forename: James P
authors.initials: JP
authors.lastname: O'Gara
authors.forename: Hilary
authors.initials: H
authors.lastname: Humphreys
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Greene
mesh_terms: D001253:Astrocytes / Q000276:immunology* / Q000382:microbiology*; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D011135:Polysaccharides, Bacterial; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C113579:polysaccharide intercellular adhesin