Toll‐like Receptor 2 Ligand–Induced Protection against Bacterial Endophthalmitis

Abstract

Activation of innate immunity plays a key role in determining the outcome of an infection. Here, we investigated whether Toll-like receptors (TLRs) are involved in retinal innate response and explored the prophylactic use of TLR2 ligand in preventing bacterial endophthalmitis. C57BL/6 mice were given intravitreal injections of Pam3Cys, a synthetic ligand of TLR2, or vehicle (phosphate-buffered saline) 24 h prior to Staphylococcus aureus inoculation. The severity of endophthalmitis was graded by slit lamp, electroretinography, histological examinations, and determination of bacterial load in the retina. The expression of cytokines/chemokines and cathelicidin-related antimicrobial peptide was assessed by enzyme-linked immunosorbent assay and Western blot, respectively. Intravitreal injections of Pam3Cys up-regulated TLR2 expression in the retina of C57BL/6 mice, and Pam3Cys pretreatment significantly improved the outcome of S. aureus endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinography in C57BL/6 mice. Furthermore, Pam3Cys pretreatment activated retinal microglia cells, induced the expression of cathelicidin-related antimicrobial peptide, and remarkably reduced the bacterial load. This is the first report that highlights the existence and role of TLR2 in retinal innate immune response to S. aureus infection and suggests that modulation of TLR activation provides a novel prophylactic approach to prevent bacterial endophthalmitis.