title: Activation of Toll-like receptors 2 and 4 in Aspergillus fumigatus keratitis.
abstract: Toll-like receptor (TLR) 2 and TLR4 are major receptors of Aspergillus fumigatus. Aspergillus fumigatus signaling in cornea induces the production of many pro-inflammatory molecules. In this study, we have shown that exposure of telomerase-immortalized human corneal epithelial cells (HCECs) to A. fumigatus antigens resulted in up-regulation of TLR2 and TLR4, and release of IL-1beta and IL-10 in HCECs, effects that could be inhibited by treatment with TLR2, and TLR4 antibodies. In addition, the A. fumigatus antigens-induced production of IL-1beta and IL-10 in supernatants of corneal epithelial cells was also attenuated by NF-kappaB inhibitor. Aspergillus fumigatus keratitis developed in Wistar rats, as evidenced by high SLE scores, influx of polymorphonuclear leukocytes (PMNs), activation of TLR2 and TLR4, and production of IL-1beta and IL-10 over controls. These findings indicate that the cornea has functional TLR2 and TLR4, and activation of TLR2 and TLR4 through NF-kappaB may contribute to pathogenesis of keratomycosis.
authors.affiliation: Department of Ophthalmology, Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
authors.lastname: Jie Zhao
authors.forename: Xin-yi
authors.initials: XY
authors.lastname: Wu
authors.forename: Fu-Shin X
authors.initials: FS
authors.lastname: Yu
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology / Q000378:metabolism; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus; D002460:Cell Line; D019573:Epithelium, Corneal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000946:Antigens, Fungal; D053583:Interleukin-1beta; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10