RGD Reference Report - Innate immune regulation of Serratia marcescens-induced corneal inflammation and infection. - Rat Genome Database

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Innate immune regulation of Serratia marcescens-induced corneal inflammation and infection.

Authors: Zhou, R  Zhang, R  Sun, Y  Platt, S  Szczotka-Flynn, L  Pearlman, E 
Citation: Zhou R, etal., Invest Ophthalmol Vis Sci. 2012 Oct 25;53(11):7382-8. doi: 10.1167/iovs.12-10238.
RGD ID: 8662876
Pubmed: PMID:23033384   (View Abstract at PubMed)
PMCID: PMC3481604   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.12-10238   (Journal Full-text)

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 x 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bacterial Keratitis  ISOIl1r1 (Mus musculus)8662876; 8662876associated with Serratia InfectionsRGD 
Bacterial Keratitis  IMP 8662876; 8662876; 8662876; 8662876; 8662876associated with Serratia InfectionsRGD 
Bacterial Keratitis  ISOLy96 (Mus musculus)8662876; 8662876associated with Serratia InfectionsRGD 
Bacterial Keratitis  ISOMyd88 (Mus musculus)8662876; 8662876associated with Serratia InfectionsRGD 
Bacterial Keratitis  ISOTlr4 (Mus musculus)8662876; 8662876associated with Serratia InfectionsRGD 
Bacterial Keratitis  ISOTlr5 (Mus musculus)8662876; 8662876associated with Serratia InfectionsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1r1  (interleukin 1 receptor type 1)
Ly96  (lymphocyte antigen 96)
Myd88  (MYD88, innate immune signal transduction adaptor)
Tlr4  (toll-like receptor 4)
Tlr5  (toll-like receptor 5)

Genes (Mus musculus)
Il1r1  (interleukin 1 receptor, type I)
Ly96  (lymphocyte antigen 96)
Myd88  (myeloid differentiation primary response gene 88)
Tlr4  (toll-like receptor 4)
Tlr5  (toll-like receptor 5)

Genes (Homo sapiens)
IL1R1  (interleukin 1 receptor type 1)
LY96  (lymphocyte antigen 96)
MYD88  (MYD88 innate immune signal transduction adaptor)
TLR4  (toll like receptor 4)
TLR5  (toll like receptor 5)


Additional Information