Toll-like receptor 2 expression on human conjunctival epithelial cells: a pathway for Staphylococcus aureus involvement in chronic ocular proinflammatory responses

Ann Allergy Asthma Immunol. 2005 Apr;94(4):486-97. doi: 10.1016/S1081-1206(10)61120-9.


Background: Staphylococcus aureus colonization is common in atopic keratoconjunctivitis, potentially activating epithelial cells via toll-like receptor 2 (TLR-2) and the receptor for platelet-activating factor (PAFR).

Objectives: To examine human conjunctival epithelial cells for the expression of TLR-2 in vitro and in vivo and to evaluate the role of TLR-2 in S aureus-mediated activation of these cells.

Methods: Conjunctival epithelial cells isolated from cadaveric tissues were stimulated with interferon gamma (IFN-gamma) or a commercial S aureus cell wall extract (Staphylococcus aureus-CWE) (with or without anti-TLR-2 blocking antibody or PAFR antagonist) and were analyzed for tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8) release; surface expression of TLR-2, intercellular adhesion molecule-1, HLA, and CD14; and TLR-2 messenger RNA expression. Ocular surface cells collected via impression cytology were examined for TLR-2 expression via flow cytometry.

Results: Expression of TLR-2 was up-regulated on conjunctival epithelial cells by IFN-gamma and Staphylococcus aureus-CWE. Expression of TLR-2 messenger RNA was increased by IFN-gamma. Staphylococcus aureus-CWE up-regulated intercellular adhesion molecule 1, HLA, and CD14 expression and increased TNF-alpha and IL-8 release in a dose-dependent manner. Anti-TLR-2 significantly inhibited TNF-alpha release, whereas PAFR antagonist significantly inhibited IL-8 release. Toll-like receptor 2 was expressed on conjunctival epithelial cells from 4 of 5 patients with atopic keratoconjunctivitis, 3 of 5 with seasonal allergies, and 0 of 3 without allergies.

Conclusions: Conjunctival epithelial cells express TLR-2 and may play an active role in the chronic ocular inflammatory response to S aureus through pathways that involve TLR-2 and PAFR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Blotting, Northern
  • Conjunctiva / immunology*
  • Conjunctiva / microbiology
  • Conjunctivitis / immunology
  • Conjunctivitis / microbiology*
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Female
  • HLA-DR Antigens / immunology
  • Humans
  • Intercellular Adhesion Molecule-1 / immunology
  • Interferon-gamma / immunology
  • Interleukin-8 / immunology
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / immunology*
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / immunology


  • HLA-DR Antigens
  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma