Elsevier

Brain Research Bulletin

Volume 81, Issues 2–3, 15 February 2010, Pages 219-228
Brain Research Bulletin

Review
Innate immunity of the ocular surface

https://doi.org/10.1016/j.brainresbull.2009.10.001Get rights and content

Abstract

The ocular surface epithelium serves a critical function as the defensive front line of the innate immune system. While the detection of microbes is arguably its most important task, an exaggerated host defense reaction to endogenous bacterial flora may initiate and perpetuate inflammatory mucosal responses. The ability of cells to recognize pathogen-associated molecular patterns (PAMPs) mainly depends on the expression of a family of Toll-like receptors (TLRs). A healthy ocular surface is not inflammatory, even though ocular surface epithelium is in constant contact with bacteria and bacterial products. In this study, we show that human ocular surface epithelial cells, both corneal and conjuctival epithelial cells, respond to viral double-stranded RNA mimic polyI:C to produce pro-inflammatory cytokines through TLR3, while they fail to respond functionally to lipopolysaccharide, a TLR4 ligand. Moreover, human ocular surface epithelium responds to flagellins from ocular pathogenic, but not ocular non-pathogenic bacteria, to produce pro-inflammatory cytokines through TLR5. Thus, ocular surface epithelial cells selectively respond to microbial components and induce limited inflammation; immune-competent cells can recognize microbial components through TLRs and induce the inflammation. The unique innate immune response of the ocular surface epithelium may contribute to its coexistence with commensal bacteria.

Inflammatory bowel disease is thought to result from an abnormal response to the gut microbiota. Thus, we also considered the possibility of an association between ocular surface inflammation and a disordered innate immune response. IκBζ is important for TLR signaling, in mice, its knock-out produced severe, spontaneous ocular surface inflammation, the eventual loss of goblet cells, and spontaneous perioral inflammation, suggesting that dysfunction/abnormality of innate immunity can lead to ocular surface inflammation.

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Acknowledgments

We thank Chie Sotozono and Junji Hamuro for their invaluable advice, and Chikako Endo for technical assistance. This work was supported in part by Grants-in-Aid for scientific research from the Japanese Ministry of Health, Labour and Welfare, the Japanese Ministry of Education, Culture, Sports, Science and Technology, CREST from JST, a research grant from the Kyoto Foundation for the Promotion of Medical Science, the Intramural Research Fund of Kyoto Prefectural University of Medicine, a

References (27)

  • S. Yamazaki et al.

    A novel IkappaB protein. IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei

    J. Biol. Chem.

    (2001)
  • J.H. Cho

    The genetics and immunopathogenesis of inflammatory bowel disease

    Nat. Rev. Immunol.

    (2008)
  • M. Karin et al.

    Phosphorylation meets ubiquitination: the control of NF-κB activity

    Annu. Rev. Immunol.

    (2000)
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