Abstract
Purpose:
To test the hypothesis that MyD88-dependent and MyD88-independent signaling pathways contribute to inflammation during Bacillus cereus endophthalmitis. TLR4 is the only TLR that can signal through both MyD88-dependent and MyD88-independent pathways to elicit an inflammatory response.Hence the role of TLR4, MyD88 and TRIF in the pathogenesis of B.cereus endophthalmitis was investigated.
Methods:
Experimental endophthalmitis was induced in TLR4-/-, MyD88-/-, TRIF-/- and wild type C57BL/6J mice by intravitreally injecting 100 CFU of B. cereus ATCC 14579. At various time points after infection, eyes were analyzed for intraocular bacterial growth, retinal function, and acute intraocular inflammation by polymorphonuclear leukocyte influx (myeloperoxidase activity), and histology. Values represent N≥4 eyes/time point, mean ± SEM.
Results:
The intraocular growth rates of B.cereus in infected eyes were determined following 4, 8 and 12 hours of infection. B. cereus grew at similar rates in infected eyes of TLR4-/-, MyD88-/- and wild type mice. But there was a significant reduction in bacterial growth rate in TRIF-/-. Retinal function loss was significantly less in TLR4-/-, TRIF-/- and MyD88-/- mice when compared to wild type mice at 8 and 12 hours following infection. Histological comparison between infected knockouts and infected wild type mice revealed a decrease in retinal architecture disruption and less inflammation in TLR4-/-, TRIF-/- and MyD88-/- when compared to wild type mice. Myeloperoxidase activity measured at different time-points in TLR4-/-, TRIF-/- and MyD88-/- indicated a significant reduction in neutrophil influx in these knockouts when compared to wild type mice.
Conclusions:
Previous studies demonstrated the importance of TLR2, a MyD88-dependent innate receptor, in inflammation and vision loss during B. cereus endophthalmitis. The results from our studies suggest that the inflammatory cascade in endophthalmitis is initiated, in part, by TLR4 that signals through MyD88-dependent and MyD88-independent TRIF signaling pathways, culminating in a sight-threatening inflammatory response against B.cereus.
Keywords: 513 endophthalmitis •
594 microbial pathogenesis: experimental studies