title: Response of corneal epithelial cells to Staphylococcus aureus.
abstract: Staphylococcus aureus is a leading cause of invasive infection. It also infects wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence exists on the expression of Toll-like receptors by human corneal epithelial cells. It was therefore of interest to determine how epithelial cells from this immune privileged tissue respond to S. aureus. Further, it was of interest to determine whether cytolytic toxins, with the potential to cause ion flux or potentially permit effector molecule movement across the target cell membrane, alter the response. Microarrays were used to globally assess the response of human corneal epithelial cells to S. aureus. A large increase in abundance of transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was observed. CCL20 release into the medium was detected, and this response was found to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to S. aureus by increasing the intracellular abundance of mRNA for inflammatory mediators, transcription factors, and genes related to MAP kinase pathways, in ways similar to other cell types. The corneal epithelial cell response was surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a stress response. Although model toxigenic and non-toxigenic strains of S. aureus were employed in the present study, the results obtained were strikingly similar to those reported for stimulation of vaginal epithelial cells by clinical toxic shock toxin expressing isolates, demonstrating that the initial epithelial cellular responses to S. aureus are largely independent of strain as well as epithelial cell tissue source.
authors.affiliation: Harvard Medical School, Boston, MA, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heimer
authors.forename: Ai
authors.initials: A
authors.lastname: Yamada
authors.forename: Hugh
authors.initials: H
authors.lastname: Russell
authors.forename: Michael
authors.initials: M
authors.lastname: Gilmore
mesh_terms: D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D019573:Epithelium, Corneal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D011506:Proteins; D012333:RNA, Messenger