Abstract
Purpose: :
This study investigated the underlying mechanisms for flagellin-induced dendritic cell recruitment and/or activation and defines their role in corneal innate defense.
Methods: :
B6.DTR/EGFP mice were used for local depletion of DCs. Diphtheria toxin (DT) was administrated subconjunctivally (50 ng in 5 μl PBS). The efficiency of DC depletion in the cornea was monitored for the disappearance of fluorescent cells. Scarified corneas of adult B6.DTR/EGFP or wt B6 mice mice were pretreated with flagellin and then inoculated with 5X103 P. aeruginosa. Disease progress was monitored by digital photograph, clinical scoring, cytokine expression determined by ELISA, bacterial counting, and PMN infiltration measured by MPO determination.
Results: :
Topical flagellin significantly increased the number of CD11c- and CD80/86-positive cells (active DCs) in scratched corneas. Local depletion of DC resulted in significant higher bacterial load compared to WT injected with DT or B6.DTR/EGFP injected with POBS at 3 dpi. The protective effects of flagellin pretreatment on bacterial clearance in DC depleted mice were diminished compared to that in wild type B6 mice.
Conclusions: :
DCs are recruited and/or activated in the corneas in response to flagellin. Deletion of DCs increased corneal susceptibility to P. aeruginosa and abolished flagellin induced protection in B6 mice. DCs play a critical role of corneal innate immunity.
Keywords: cornea: epithelium • inflammation • keratitis