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

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.