Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells

J Neuroimmunol. 2004 Aug;153(1-2):7-15. doi: 10.1016/j.jneuroim.2004.04.018.

Abstract

Toll-like receptors (TLRs) are crucial components of innate immunity that participate in host defense against microbial pathogens. We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. Real time PCR analysis revealed gene expression for TLRs 1-7, 9, and 10 in RPE cells. TLRs 1 and 3 were the most highly expressed TLRs. Protein expression for TLRs 2, 3, and 4 was observed on RPE cells and this expression was augmented by treatment with poly I:C or interferon-gamma (IFN-gamma). TLR 3 is the receptor for dsRNA, an intermediate of virus replication. Because RPE cells express TLR 3 and are frequently the site of virus replication within the retina, we evaluated TLR 3 signaling. RPE cells treated with poly I:C produced IFN-beta but not IFN-alpha, and this was inhibited by the treatment of RPE cells with anti-TLR 3 antibody. Human recombinant IFN-beta was shown to be biologically active on RPE cells by inhibiting viral replication. Poly I:C treatment of RPE resulted in an increase in the production of IL-6, IL-8, MCP-1, and sICAM-1. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies / pharmacology
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique / methods
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunity, Innate / physiology*
  • Immunoenzyme Techniques / methods
  • Interferon Inducers / pharmacology
  • Interferon-beta / metabolism
  • Interferon-beta / pharmacology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Monocytes / metabolism
  • Pigment Epithelium of Eye / immunology*
  • Poly I-C / pharmacology
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Retina / cytology
  • Retina / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Signal Transduction / immunology*
  • Toll-Like Receptor 3
  • Toll-Like Receptors

Substances

  • Antibodies
  • Cell Adhesion Molecules
  • Chemokines
  • Cytokines
  • Interferon Inducers
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Interferon-beta
  • Poly I-C