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Infection and Immunity, January 2008, p. 89-96, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.01232-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Flagellin Suppresses the Inflammatory Response and Enhances Bacterial Clearance in a Murine Model of Pseudomonas aeruginosa Keratitis{triangledown}

Ashok Kumar,1,2 Linda D. Hazlett,2 and Fu-Shin X. Yu1,2*

The Kresge Eye Institute/Department of Ophthalmology,1 Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 482012

Received 7 September 2007/ Accepted 3 October 2007

Pseudomonas aeruginosa is a common organism associated with bacterial keratitis, especially in extended-wear contact lens users. In the present study, we determined that pretreatment of cultured human corneal epithelial cells with flagellin isolated from the P. aeruginosa PAO1 strain attenuated cytokine production when the cells were challenged with a cytotoxic strain (ATCC 19660), suggesting a potential use of bacterial flagellin to downregulate infection-associated inflammation in vivo. Administration of flagellin via the subconjunctival and intraperitoneal routes 24 h prior to Pseudomonas inoculation significantly improved the disease outcome, preserved structural integrity and transparency, and thus maintained vision in otherwise perforated corneas of C57BL/6 (B6) mice. The flagellin pretreatment resulted in suppression of polymorphonuclear leukocyte infiltration at a late stage of infection but not at an early stage of infection, decreased the expression of proinflammatory cytokine genes (genes encoding interleukin-1β [IL-1β], macrophage inflammatory protein 2, IL-12, and gamma interferon), and greatly enhanced bacterial clearance in the corneas of B6 mice probably through induced expression of the cathelicidin-related antimicrobial peptide and inducible nitric oxide synthase. This is the first report that describes the protective mechanisms induced by a Toll-like receptor agonist that not only curbs the host inflammatory response but also eliminates invading bacteria in the B6 mouse cornea.

* Corresponding author. Mailing address: Kresge Eye Institute, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI 48201. Phone: (313) 577-1657. Fax: (313) 577-7781. E-mail: fyu{at}med.wayne.edu

{triangledown} Published ahead of print on 15 October 2007.

Editor: F. C. Fang

Infection and Immunity, January 2008, p. 89-96, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.01232-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mun, J. J., Tam, C., Kowbel, D., Hawgood, S., Barnett, M. J., Evans, D. J., Fleiszig, S. M. J. (2009). Clearance of Pseudomonas aeruginosa from a Healthy Ocular Surface Involves Surfactant Protein D and Is Compromised by Bacterial Elastase in a Murine Null-Infection Model. Infect. Immun. 77: 2392-2398 [Abstract] [Full Text]  


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