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C. Hackett, E. Whiston, N. Sugi, B. R. Ksander, M. S. Gilmore, M. S. Gregory; Resistance to Infection and Protection of Retinal Tissue During S. aureus Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):837.
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© ARVO (1962-2015); The Authors (2016-present)
Endophthalmitis is a bacterial infection of the posterior of the eye that can lead to complete vision loss. The purpose of our investigation was to identify components of innate immunity that: (i) clear the infection, and (ii) protect host tissues from non-specific damage. We demonstrated previously that Fas ligand (FasL) was critical for bacterial clearance in C57BL/6 mice infected with S. aureus. Interestingly, there are two FasL allotypes expressed in mice; C57BL/6 mice (FasL.1) and BALB/c mice (FasL.2). Fas/FasL binding is more effective in FasL.2 mice. Therefore, we hypothesized that BALB/c mice are more resistant to S. aureus-induced endophthalmitis.
C57BL/6, BALB/c, and BALB/c-gld/gld mice received intravitreal injections of 2500 CFU of S. aureus (RN6390). Clinical examinations, and bacterial quantification were performed at 24, 48, 72, and 96 hours post injection. Retinal damage was assessed by electroretinalgraphy (ERG) and histology. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration.
C57BL/6 mice infected with 2500 CFU S. aureus developed a progressive infection that resulted in complete destruction of the eye in 80% of the mice, as determined by clinical exams, ERG, and histology. By contrast, BALB/c mice displayed increased resistance to infection and complete destruction occurred in only 25% of the mice. In addition, in mice that successfully cleared the infection, (75% of BALB/c and 20% of C57BL/6) BALB/c mice displayed decreased retinal damage and increased retinal function. Bacterial quantification at 48 hours revealed a delay in bacterial clearance in C57BL/6 mice (3 x 107 CFU/eye) as compared to BALB/c mice (1 x 105 CFU/eye). This corresponded with a decreased neutrophil infiltrate in C57BL/6 mice as compared to BALB/c mice. To our surprise, FasL defective BALB/c mice (gld/gld) showed no difference in their ability to clear the infection as compared with wild-type BALB/c mice. However, ERG analysis and histology revealed increased retinal damage and significant loss of retinal function occurred in the absence of FasL.
We conclude that BALB/c mice display a more rapid and robust neutrophil mediated innate immune response to S. aureus as compared with C57BL/6 mice, resulting in rapid bacterial clearance and increased resistance to S. aureus endophthalmitis. Furthermore, these studies demonstrate that while the mechanisms responsible for improved bacterial clearance in BALB/c mice are Fas ligand independent, Fas ligand is required for protecting the host tissue from nonspecific damage.
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