April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Pretreatment with Toll-like Receptor Agonist Induces Tolerance Against Corneal Aspergillus Fumigatus Infection In Vitro and In Vivo
Author Affiliations & Notes
  • Xinyi Wu
    Ophthal QiLu Hosp/Ophthal,
    Shandong University, Jinan, Shandong, China
  • Jun Wang
    Ophthal QiLu Hosp/Ophthal,
    Shandong University, Jinan, Shandong, China
  • XiaoYan Zhang
    Shandong University, Jinan, Shandong, China
  • LeYi Wang
    Ophthal QiLu Hosp/Ophthal,
    Shandong University, Jinan, Shandong, China
  • Footnotes
    Commercial Relationships  Xinyi Wu, None; Jun Wang, None; XiaoYan Zhang, None; LeYi Wang, None
  • Footnotes
    Support  National Natural Science Foundation of China (No.30571997, 30872807)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1208. doi:
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      Xinyi Wu, Jun Wang, XiaoYan Zhang, LeYi Wang; Pretreatment with Toll-like Receptor Agonist Induces Tolerance Against Corneal Aspergillus Fumigatus Infection In Vitro and In Vivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1208.

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

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Abstract

Purpose: : To evaluate the function of Toll-like receptor (TLR) agonist pretreatment in reducing Aspergillus fumigatus (Af) induced corneal inflammation and the underlying molecular mechanism in vitro and in vivo.

Methods: : Telomerase-immortalized human stroma fibroblasts (THSFs) and Wistar rats were pretreated with low-dose TLR4 agonist lipopolysaccharide (LPS) or TLR2 agonist Zymosan respectively for various times and then challenged with a high dose of Af. At various time points postinfection, cytokines (IL8, IL6, TNFα, IL1β), antimicrobial peptides (CCL20, Tβ4, rBD2), TLR4, TLR2, MyD88 and IΚBαexpression were assayed by real time RT-PCR, ELISA and Immunohistochemistry staining. PMN migration was assayed using 24-well Transwell filters and Myeloperoxidase activity was assessed for the quantification of PMN infiltration. For blocking experiments, IL6 expression was measured by ELISA with an anti-TLR4 mAb antibody. Slit lamp and clinical scoring were performed and corneas were analyzed for histopathological changes.

Results: : Pretreatment of THSFs with low-dose LPS resulted in diminished production of IL8, IL6, TLR4 and MyD88, elevated expression of CCL20, Tβ4 and IΚBα, and suppression of PMN migration upon subsequent Af challenge. TLR4 blocking induced upregulation of IL6 in LPS pretreated group and no significant difference was found compared with control. Zymosan administration prior to rat corneal fungal infection significantly improved disease outcome, resulted in the suppression of PMN infiltration in late, decreased the expression of TNFα, IL1β and TLR2 , and greatly enhanced fungal clearance and expression of rBD2 in corneas.

Conclusions: : TLR agonist pretreatment could induce corneal antifungal tolerance and reduce fungal inflammation by boosting the body's own innate defense system. The downregulation of TLR and MyD88 and upregulation of IΚBαmay play significant roles in modulating corneal antifungal tolerance.

Keywords: cornea: basic science • fungal disease 
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