June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Chitinase 3-like-1 Promotes Candida albicans Killing and Preserves Corneal Structure and Function by Controlling Host Antifungal Responses
Author Affiliations & Notes
  • Nan Gao
    Ophthalmology, Wayne State Univ/Kresge Eye Inst, Detroit, MI
  • Fushin X Yu
    Ophthalmology, Wayne State Univ/Kresge Eye Inst, Detroit, MI
  • Footnotes
    Commercial Relationships Nan Gao, None; Fushin Yu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1879. doi:
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    • Get Citation

      Nan Gao, Fushin X Yu; Chitinase 3-like-1 Promotes Candida albicans Killing and Preserves Corneal Structure and Function by Controlling Host Antifungal Responses. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1879.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To elucidate the role of chitinase 3-like 1 (Chi3l1), a conserved prototypic chitinase-like protein, in controlling corneal innate immune response to Candida albicans (CA) infection in C47BL/6 mice.

Methods: Scarified B6 mouse corneas were pretreated with flagellin and then inoculated with 105 C. albicans. At 6 hpi, epithelial cells were scraped off the cornea and chi3l1 expression was detected by PCR and immunohistochemistry. The function of Chi3l1 was determined by applying recombinant protein or siRNA subconjunctivally prior to C. albicans inoculation. Disease progress was monitored by digital photograph, ELISA determination of cytokine expression, and MPO measurement for PMN infiltration. Cryostat sections of mouse corneas were immunostained with antibodies against CXCL10 and CXCR3. For the NF-κB inhibition experiment, human corneal epithelial cells were pretreated with NF-κB inhibitor (kamebakaurin) for 30 min before stimulating with 200ng/ml CHI3L1. IκB-α, p-IκB-α and CXCL10 were determined by Western blotting or dot blotting.

Results: Flagellin-pretreatment markedly induced Chi3l1 expression, coinciding with greatly enhanced innate immunity against CA keratitis in B6 mouse corneas. While CA keratitis was more severe in the corneas treated with Chi3l1 siRNA, the cornea treated with recombinant Chi3l1 had greatly reduced fungal burden, markedly decreased PMN infiltration, and much reduced expression of CXCL2. Chi3l1 treatment resulted in the induction of CXCL10 and IL-17c in corneal epithelial cells. Exposure of human corneal epithelial cells to Chi3l1 induced CXCL10 expression in a NF-κB dependent manner.

Conclusions: These data demonstrate that Chi3l1 is induced during infection, where it promotes fungal clearance and regulates the appropriateness and intensity of antifungal innate immune responses in the cornea.<br />

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