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J Infect Dis. 2010 Jan 15;201(2):255-63. doi: 10.1086/649589.

Toll-like receptor 2 ligand-induced protection against bacterial endophthalmitis.

Author information

  • 1The Kresge Eye Institute-Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. akuma@med.wayne.edu

Abstract

BACKGROUND:

Activation of innate immunity plays a key role in determining the outcome of an infection. Here, we investigated whether Toll-like receptors (TLRs) are involved in retinal innate response and explored the prophylactic use of TLR2 ligand in preventing bacterial endophthalmitis.

METHODS:

C57BL/6 mice were given intravitreal injections of Pam3Cys, a synthetic ligand of TLR2, or vehicle (phosphate-buffered saline) 24 h prior to Staphylococcus aureus inoculation. The severity of endophthalmitis was graded by slit lamp, electroretinography, histological examinations, and determination of bacterial load in the retina. The expression of cytokines/chemokines and cathelicidin-related antimicrobial peptide was assessed by enzyme-linked immunosorbent assay and Western blot, respectively.

RESULTS:

Intravitreal injections of Pam3Cys up-regulated TLR2 expression in the retina of C57BL/6 mice, and Pam3Cys pretreatment significantly improved the outcome of S. aureus endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinography in C57BL/6 mice. Furthermore, Pam3Cys pretreatment activated retinal microglia cells, induced the expression of cathelicidin-related antimicrobial peptide, and remarkably reduced the bacterial load.

CONCLUSIONS:

This is the first report that highlights the existence and role of TLR2 in retinal innate immune response to S. aureus infection and suggests that modulation of TLR activation provides a novel prophylactic approach to prevent bacterial endophthalmitis.

PMID:
19995266
[PubMed - indexed for MEDLINE]
PMCID:
PMC2798006
Free PMC Article
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