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Xiaoyong Yuan, Kirk R. Wilhelmus; Toll-like Receptors Involved in the Pathogenesis of Experimental Candida albicans Keratitis. Invest. Ophthalmol. Vis. Sci. 2010;51(4):2094-2100. doi: 10.1167/iovs.09-4330.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the expression and function of toll-like receptors (TLRs) during experimental keratomycosis.
Scarified corneas of BALB/c mice were topically inoculated with Candida albicans and compared with control corneas by a murine gene microarray and immunostaining. Real-time reverse transcription polymerase chain reaction (RT-PCR) determined relative TLR gene expression in murine and human donor corneas. The scarified corneas of TLR2−/− mice, TLR4−/− mice, and C57BL/6J control mice were also inoculated with C. albicans, to determine relative severity, fungal load, and cytokine transcript levels.
TLR1, -2, -4, -6, and -13 were significantly upregulated (5- to 10-fold; P < 0.01) by microarray, and TLR1, -2, -4, and -13 were significantly increased (4- to 11-fold; P < 0.05) by real-time RT-PCR in BALB/c murine corneas. Similarly, TLR2, -6, and -13 were significantly upregulated (5- to 16-fold; P ≤ 0.001) by real-time RT-PCR in C57BL/6J murine corneas the day after inoculation, and TLR2 and -13 remained significantly (P < 0.05) increased after 1 week. TLR2 transcript was also upregulated twofold (P = 0.04) in C. albicans–inoculated explanted human corneas. Although murine keratitis severity scores were similar, significantly more fungi were recovered from TLR2−/− mouse corneas (P = 0.04) than from TLR4−/− mouse corneas (P = 0.9). Tumor necrosis factor-α, interleukin 23, chemokine C-C ligands 3 and 4, and dectin-1 were significantly (P < 0.05) downregulated in C. albicans–infected corneas of TLR2−/− mice.
TLR2 signals proinflammatory cytokines that control fungal growth during C. albicans keratitis. TLR13 may have an additional role in the innate immune response of murine corneal candidiasis.
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