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N. A. Tullos, E. Norcross, S. Taylor, Q. C. Moore, III, M. E. Sanders, M. E. Marquart; Toll-Like Receptor 4, But Not Toll-Like Receptor 2, is Necessary for Protection Against Corneal Damage During Pneumococcal Keratitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3441.
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Host Toll-Like Receptors (TLRs) 2 and 4 have been reported to be bound and activated by Gram Positive bacteria (TLR 2) and the Streptococcus pneumoniae virulence factor, pneumolysin (TLR 4). Because TLRs 2 and 4 are present on corneal epithelial cells, and because pneumolysin has been reported to be an important virulence factor in pneumococcal keratitis, the objective of this study was to characterize the roles of TLR 2 and TLR 4 in pneumococcal keratitis.
The scarified corneas of C57BL/6 (wild type), TLR2 -/- and TLR -/- mice (C57BL/6 background) were inoculated with 108 colony forming units (CFU) S. pneumoniae clinical keratitis strain K1263. Clinical examinations were performed once per day on days 1-21 post infection (p.i.) for each eye. Mice were sacrificed on days 1 and 3 p.i. to quantify the bacterial CFU from each eye.
The mean bacterial CFU recovered from the eyes of TLR 2 -/- (4.725 ± 0.1897 log10 CFU)1 day p.i. were significantly higher than the CFU recovered from the wild type mice (0.850 ± 0.850 log10 CFU; P = 0.016;N=4 per group). The CFU recovered from TLR 4 -/- mice (2.89 ± 0.978 log10 CFU), however, were not significantly different from the wild type mice (P= 0.270; N=4). All eyes from all groups were sterile by 72 hours p.i. Mean clinical scores for the corneas of TLR 4 -/- mice (N=12) were significantly higher compared to the scores of the wild type mice (N=19) at every time point excluding day 1 and day 4 (P≤0.01). The corneas of the TLR 4 -/- mice appeared heavily scarred following infection and throughout all 21 days. Clinical scores for the corneas of TLR 2 -/- mice (N=8) were not significantly different from wild type scores at any time point (P≥0.090).
These data suggest that TLR 4 is likely critical to the ability of the host to prevent irreversible corneal damage during pneumococcal keratitis. In contrast, TLR 2 appears to have a diminished role except for bacterial clearance.
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