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Proinflammatory chemokines during Candida albicans keratitis
Xiaoyong Yuan1, Xia Hua, Kirk R Wilhelmus
1Sid W. Richardson Ocular Microbiology Laboratory, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin St., Houston, TX 77030, USA.
Experimental Eye Research
|December 17, 2009
Summary
Chemokines, particularly CC chemokine ligand 3 (CCL3), are crucial in the early inflammatory response to Candida albicans eye infections. Inhibiting CCL3 reduced infection severity and inflammation but did not affect fungal load.
Area of Science:
- Immunology
- Ophthalmology
- Microbiology
Background:
- Leukocyte recruitment to infected tissues is mediated by chemotactic cytokines called chemokines.
- Understanding chemokine roles in fungal keratitis is vital for developing targeted therapies.
- Candida albicans is a common cause of infectious keratitis, leading to significant vision impairment.
Purpose of the Study:
- To investigate the chemokine profile during experimental Candida albicans keratitis in mice.
- To determine the impact of chemokine inhibition on leukocyte infiltration and fungal growth.
- To assess the effect of CCL3 inhibition on associated cytokine expression.
Main Methods:
- Murine model of Candida albicans keratitis established via corneal scarification.
- Gene microarray analysis identified upregulated chemokines; RT-PCR and immunostaining confirmed expression.
- Subconjunctival administration of anti-chemokine antibody (anti-CCL3) evaluated clinical outcomes.
Main Results:
- Microarray revealed significant upregulation of 6 CC and 6 CXC chemokines.
- Chemokine (CC-motif) ligand 3 (CCL3) showed a 108-fold increase within 24 hours post-infection.
- Anti-CCL3 treatment reduced clinical severity, corneal neovascularization, and inflammatory cell infiltration, but not fungal recovery.
- CCL3 inhibition significantly decreased tumor necrosis factor and interleukin-1beta expression.
Conclusions:
- Chemokines, especially CCL3, are critical mediators of the acute inflammatory response in C. albicans keratitis.
- Targeting CCL3 may offer a therapeutic strategy to manage inflammation in fungal keratitis.
- Further research is warranted to explore the therapeutic potential of chemokine inhibition in ocular infections.
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