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E.A. Whiston, N. Sugi, M. Engelbert, M.S. Gilmore, B.R. Ksander, M.S. Gregory; Host Resistance to Staphylococcus aureus Endophthalmitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1915.
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Endophthalmitis is a bacterial infection of the posterior segment of the eye that is either cleared by the host's immune system, or develops into a severe infection that destroys the eye. We previously demonstrated that C57BL/6J mice cleared a 500 CFU intravitreal inoculation of Staphylococcus aureus, but C57BL/6J FasL–defective gld mice failed to clear an identical infection. Thus, C57BL/6J mice possessed a FasL–dependant resistance to destructive endophthalmitis. Interestingly, there are two FasL allotypes expressed in mice; C57BL/6J mice express FasL.1 and BALB/c mice express FasL.2. FasL.2 exhibits significantly greater cytotoxic activity, indicating that the Fas/FasL system works more efficiently in FasL.2 mice. Given the importance of FasL in resistance to endophthalmitis in C57BL/6J mice, we hypothesized that BALB/c mice, which express the stronger FasL.2 allotype, would be more resistant to S. aureus–induced endophthalmitis.
BALB/c and C57BL/6J mice received 500, 2500, or 5000 CFU intravitreal inoculations of S. aureus. Mice were clinically evaluated by slit lamp at 24, 48, 72, and 96 hours. At 96 hours, infected eyes were enucleated and histological analysis was performed.
Both C57BL/6J and BALB/c mice cleared 500 CFU of S. aureus, while 5000 CFU resulted in destructive endophthalmitis. Although both BALB/c and C57BL/6J mice cleared 2500 CFU of S. aureus, C57BL/6J mice demonstrated more extensive inflammation and retinal damage as compared to BALB/c mice. This indicates that BALB/c mice are more resistant to S. aureus endophthalmitis. To determine whether this increased resistance was due to FasL, BALB/c FasL knockout mice received a 500 CFU inoculation of S. aureus. Unexpectedly, the loss of FasL did not eliminate the host's resistance, and 83% of BALB/c FasL knockout mice cleared the infection.
We conclude that BALB/c mice demonstrate increased resistance to S. aureus, and that this resistance is independent of FasL. These data imply that other components of the innate immune system are critical to BALB/c resistance to S. aureus endophthalmitis.
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