title: Increased resistance to Staphylococcus aureus endophthalmitis in BALB/c mice: Fas ligand is required for resolution of inflammation but not for bacterial clearance.
abstract: FasL was recently shown be required for bacterial clearance in C57BL/6 mice that express the FasL.1 allotype. The FasL.2 allotype is expressed in BALB/c mice and exhibits increased binding affinity to and increased cytotoxic activity against Fas(+) target cells. Therefore, we hypothesized that BALB/c mice would be more resistant to Staphylococcus aureus-induced endophthalmitis. To test this hypothesis, C57BL/6, BALB/c, and BALB(gld) mice received intravitreal injections of 2,500 CFU of S. aureus (RN6390). Clinical examinations, electroretinography (ERG), histology, and bacterial quantification were performed at 24, 48, 72, and 96 h postinjection. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration. At 96 h postinfection, 86% of C57BL/6 mice presented with complete destruction of the eye, compared to only 29% of BALB/c mice with complete destruction. To our surprise, in the absence of Fas ligand, BALB(gld) mice showed no difference in bacterial clearance compared to BALB/c mice. However, histology and ERG analysis revealed increased retinal damage and significant loss of retinal function. MPO analysis revealed equal numbers of neutrophils in BALB(gld) and BALB/c mice at 24 h postinfection. However, at 48 h, the neutrophil numbers remained significantly elevated in BALB(gld) mice, correlating with the increased retinal damage observed in BALB(gld) mice. We conclude that the increased resistance to S. aureus induced endophthalmitis in BALB/c mice is not dependent upon the FasL. However, in contrast to C57BL/6 mice, FasL is required for resolution of inflammation and protecting host tissue from nonspecific damage in BALB/c mice.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Norito
authors.initials: N
authors.lastname: Sugi
authors.forename: Emily A
authors.initials: EA
authors.lastname: Whiston
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Ksander
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Gregory
mesh_terms: D000818:Animals; D009877:Endophthalmitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000473:pathology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus
chemical_list: D053222:Fas Ligand Protein; D009195:Peroxidase