Toll-like receptors (TLRs) are key components of innate immunity that detect microbial
infection and trigger host defense responses. However, they are capable of initiating both protective and damaging immune responses, as exaggerated expression of inflammatory components can have devastating effects on the host. We previously reported that TLR2 in corneal epithelium has an important role in the pathogenesis of fungal
keratitis, however, how the corneal
inflammation is modulated remains to be elucidated. This study aims to investigate the effect of targeting TLR2 on Aspergillus fumigatus
keratitis in rats. The control or TLR2
small interfering RNA (
siRNA) was applied sub-conjunctively and topically to the cornea. TLR2 immunostaining was performed to determine the feasibility of TLR2
siRNA delivery. Production of inflammatory
cytokines and
chemokines were determined by real-time quantitative PCR. Polymorphonuclear leukocyte (PMN) infiltration was assessed by
myeloperoxidase activity. It was found that rat corneas treated with TLR2
siRNA showed a significant reduction of TLR2 expression in corneal epithelium. TLR2
siRNA treatment improved the outcome of
keratitis, which was characterized by decreased
corneal opacity, less
corneal perforation, suppressed PMN infiltration, reduced production of inflammatory
cytokines and
chemokines, and less fungal burden. In conclusion, TLR2
siRNA treatment attenuated A. fumigatus
keratitis by suppressing corneal
inflammation and preventing fungal invasion, suggesting a novel avenue to control
fungal infection and avert damage caused by excessive
inflammation.