Topical flagellin-mediated innate defense against Candida albicans keratitis

Area of Science:

• Ophthalmology
• Immunology
• Microbiology

Background:

• Corneal infections, such as Candida keratitis, pose a significant threat to vision.
• The innate immune system plays a crucial role in defending the cornea against microbial invasion.
• Toll-like receptor-5 (TLR5) recognizes bacterial flagellin, a key component of the innate immune response.

Purpose of the Study:

• To investigate if flagellin, the ligand for TLR5, can induce an innate defense sufficient to protect injured corneas from Candida albicans.
• To determine the role of TLR5, cathelicidin-related antimicrobial peptide (Camp), and polymorphonuclear leukocytes (PMNs) in flagellin-mediated corneal defense.

Main Methods:

• Mice (B6, TLR5(-/-), Camp(-/-)), or PMN-depleted mice, had scarified corneas pretreated with Pseudomonas aeruginosa flagellin or a mutant, followed by C. albicans inoculation.
• Disease progression was monitored using digital photography and clinical scoring.
• Cytokine and Camp expression, PMN infiltration, fungal burden, and corneal tissue inflammation were assessed using ELISA, Western blot, MPO determination, and immunohistochemistry.

Main Results:

• Topical flagellin conferred significant protection against Candida keratitis in a TLR5-dependent manner.
• Flagellin treatment led to reduced fungal burden, decreased tissue inflammation, and accelerated functional recovery in infected corneas.
• While both PMN infiltration and Camp upregulation contributed to fungal clearance, Camp ablation abolished, and PMN depletion partially reduced, flagellin's protective effect.

Conclusions:

• Flagellin effectively induces a robust innate defense, enhancing corneal resistance to C. albicans infection.
• Topical flagellin or its mimetics show potential as prophylactic agents against microbial keratitis, particularly following contact lens wear or ocular trauma.