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A. Kumar, C. N. Singh, T. H. Mahmoud, F.-S. X. Yu; Toll-like Receptor 2 Agonist Pretreatment Protects Mice From Staphylococcus Aureus-induced Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4287.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the role of Toll-like receptor 2 (TLR2) in mediating retinal innate immune response to Staphylococcus(S.) aureus and to understand the potential protective mechanisms evoked by TLR2 ligand pretreatment.
C57BL/6 (B6) mice were given intravitreal injection of TLR2 ligand Pam3Cys or vehicle (PBS) and the retinal innate responses to TLR2 ligand including the expression of cytokines and antimicrobial peptides were assessed using ELISA and Western blot analysis, respectively. Bacterial infection was carried out by intravitreal injection of 5000 colony-forming units (CFU) of S. aureus 24 hrs post-Pam3Cys treatment. The severity of endophthalmitis was graded by slit lamp examination (SLE) at 1, 2 and 3 days post-infection (dpi). Retinal function was assessed by ERG. The eyes were extracted for histological examination of retinal damage and inflammation. Bacterial load in the retina was determined by standard bacterial plate count.
Compare to PBS control, Pam3Cys at low dosage (0.1 and 0.25 µg /eye) caused an increase in the levels of interleukin-1beta (IL-1β) and macrophage inflammatory protein 2 (MIP-2) within 6-12h. By 24 h, there was no clinically detected inflammation and cytokine levels were reduced to baseline. Unlike the induced expression of proinflammatory, Pam3cys also induced the persistent up-regulation of antimicrobial peptide CRAMP 24h post challenge. Slit-lamp, histopathological and ERG analysis revealed that intravitreal injection of Pam3Cys 24 h prior to bacterial inoculation significantly improved the severity of endophthalimitis, preserved structural integrity and architecture of the retina, and thus maintained normal retinal function. Furthermore, Pam3Cys pretreatment induced the activation of retinal microglia cells and markedly reduced the bacterial load in the retina of B6 mice.
This is the first report that highlights the importance of TLR2 in retinal innate immune response to S. aureus infection and suggests that triggering TLR activation prior to infection provides a novel prophylactic approach to prevent bacterial endophthalimitis.
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