title: Innate immune regulation of Serratia marcescens-induced corneal inflammation and infection.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Sean
authors.initials: S
authors.lastname: Platt
authors.forename: Loretta
authors.initials: L
authors.lastname: Szczotka-Flynn
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
mesh_terms: D000818:Animals; D003315:Cornea / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015818:Eye Infections, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007113:Immunity, Innate; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D016868:Serratia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012706:Serratia marcescens / Q000472:pathogenicity*