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Innate Immunity
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Activation of Toll-like receptors 2 and 4 in Aspergillus fumigatus keratitis

Jie Zhao

Department of Ophthalmology, Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China, Department of Ophthalmology, Shandong Provincial Hospital, Shandong University, Jinan, China

Xin-yi Wu

Department of Ophthalmology, Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China, xywu8868{at}163.com

Fu-Shin X. Yu

The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, USA

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-1β 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-1β and IL-10 in supernatants of corneal epithelial cells was also attenuated by NF-{kappa}B 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-1β and IL-10 over controls. These findings indicate that the cornea has functional TLR2 and TLR4, and activation of TLR2 and TLR4 through NF-{kappa}B may contribute to pathogenesis of keratomycosis.

Key Words: Toll-like receptors • Aspergillus fumigatus • cytokines • NF-kappaB • keratitis

Innate Immunity, Vol. 15, No. 3, 155-168 (2009)
DOI: 10.1177/1753425908101521


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