Staphylococcus aureus-induced corneal inflammation is dependent on Toll-like receptor 2 and myeloid differentiation factor 88.
Toll-like receptors (TLRs) expressed by the corneal epithelium represent a first line of host defense to microbial keratitis. The current study examined the role of TLR2, TLR4, and TLR9 and the common adaptor molecule myeloid differentiation factor 88 (MyD88) in a Staphylococcus aureus model of corneal inflammation. The corneal epithelia of C57BL/6, TLR2(-/-), TLR4(-/-), TLR9(-/-), and MyD88(-/-) mice were abraded using a trephine and epithelial brush and were exposed to heat- or UV-inactivated S. aureus clinical strain 8325-4 and other clinical isolates. Corneal thickness and haze were measured by in vivo confocal microscopy, neutrophil recruitment to the corneal stroma was quantified by immunohistochemistry, and cytokine production was measured by enzyme-linked immunosorbent assay. The exposure of corneal epithelium to S. aureus induced neutrophil recruitment to the corneal stroma and increased corneal thickness and haze in control C57BL/6 mice but not in TLR2(-/-) or MyD88(-/-) mice. The responses of TLR4(-/-) and TLR9(-/-) mice were similar to those of C57BL/6 mice. S. aureus-induced cytokine production by corneal epithelial cells and neutrophils was also significantly reduced in TLR2(-/-) mice compared with that in C57BL/6 mice. These findings indicate that S. aureus-induced corneal inflammation is mediated by TLR2 and MyD88 in resident epithelial cells and infiltrating neutrophils.
Sun
Yan
Y
Department of Ophthalmology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7286, USA.
Hise
Amy G
AG
Kalsow
Carolyn M
CM
Pearlman
Eric
E
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D019573:Epithelium, Corneal / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007634:Keratitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D019743:Chemokines, CXC; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9