PURPOSE: Serratia marcescens is frequently isolated from lenses of patients with contact lens-associated corneal infiltrates. In the current study, we examined the role of toll-like receptors (TLRs) and interleukin-1 receptor type 1 (IL-1R1) in S. marcescens-induced corneal inflammation and infection. METHODS: The central corneal epithelium of C57BL/6 and gene knockout mice was abraded, and 1 × 10(7) S. marcescens were added in the presence of a silicone hydrogel contact lens, and we examined corneal inflammation by confocal microscopy and neutrophil enumeration. Viable bacteria were quantified by colony-forming units (CFU). RESULTS: S. marcescens induced neutrophil recruitment to the corneal stroma, and increased corneal thickness and haze in C57BL/6 mice. Conversely, CFU was significantly lower by 48 hours post infection. In contrast, MyD88(-/-), IL-1R(-/-), TLR4(-/-), and TLR4/5(-/-) corneas infected with S. marcescens had significantly increased CFU, indicating impaired clearance. However, there was no significant difference in CFU among C57BL/6, TIRAP(-/-), and TRIF(-/-) mice. Tobramycin-killed S. marcescens induced corneal inflammation in C57BL/6 mice, which was impaired significantly in MD-2(-/-) mice and in C57BL/6 mice pretreated topically with the MD-2 antagonist eritoran tetrasodium. CONCLUSIONS: S. marcescens induces corneal inflammation by activation of TLR4/MD-2/MyD88 and the IL-1R1/MyD88 pathways, which are potential therapeutic targets for inhibition of S. marcescens-induced corneal inflammation.
PURPOSE:Serratia marcescens is frequently isolated from lenses of patients with contact lens-associated corneal infiltrates. In the current study, we examined the role of toll-like receptors (TLRs) and interleukin-1 receptor type 1 (IL-1R1) in S. marcescens-induced corneal inflammation and infection. METHODS: The central corneal epithelium of C57BL/6 and gene knockout mice was abraded, and 1 × 10(7) S. marcescens were added in the presence of a silicone hydrogel contact lens, and we examined corneal inflammation by confocal microscopy and neutrophil enumeration. Viable bacteria were quantified by colony-forming units (CFU). RESULTS:S. marcescens induced neutrophil recruitment to the corneal stroma, and increased corneal thickness and haze in C57BL/6 mice. Conversely, CFU was significantly lower by 48 hours post infection. In contrast, MyD88(-/-), IL-1R(-/-), TLR4(-/-), and TLR4/5(-/-) corneas infected with S. marcescens had significantly increased CFU, indicating impaired clearance. However, there was no significant difference in CFU among C57BL/6, TIRAP(-/-), and TRIF(-/-) mice. Tobramycin-killed S. marcescens induced corneal inflammation in C57BL/6 mice, which was impaired significantly in MD-2(-/-) mice and in C57BL/6 mice pretreated topically with the MD-2 antagonist eritoran tetrasodium. CONCLUSIONS:S. marcescens induces corneal inflammation by activation of TLR4/MD-2/MyD88 and the IL-1R1/MyD88 pathways, which are potential therapeutic targets for inhibition of S. marcescens-induced corneal inflammation.
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