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Infection and Immunity, May 2007, p. 2325-2332, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01404-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Tear Fluid Protects against Pseudomonas aeruginosa Keratitis in a Murine Experimental Model{triangledown}

Mary S. F. Kwong,1 David J. Evans,1,4 Minjian Ni,1,2 Brigitte A. Cowell,1 and Suzanne M. J. Fleiszig1,2,3*

School of Optometry, University of California, Berkeley, California 94720,1 Vision Science Program, University of California, Berkeley, California 94720,2 Graduate Groups in Microbiology and Infectious Disease, University of California, Berkeley, California 94720,3 College of Pharmacy, Touro University-California, Vallejo, California 945924

Received 31 August 2006/ Returned for modification 9 November 2006/ Accepted 12 February 2007

Pseudomonas aeruginosa keratitis is an acute sight-threatening infection. We previously reported that human tear fluid could protect individual human corneal epithelial cells in vitro against invasion by and cytotoxicity due to clinical and laboratory isolates of P. aeruginosa and that the protective mechanism was independent of bacteriostatic activity. In the present study, we examined the effects of human tear fluid in vivo. Tears were collected from healthy human volunteers and were studied in vivo in mice. The effects on the virulence of both invasive and cytotoxic clinical isolates of P. aeruginosa were examined. Tear fluid was found to reduce the severity of disease when corneas were challenged with cytotoxic bacteria immediately after scratch injury, and it completely protected against susceptibility to infection by a cytotoxic strain in a model in which corneas were infected during the healing process 6 h after scratching. Visible protection correlated with the inhibition of bacterial colonization 1, 4, and 48 h postinoculation. Tear fluid also significantly reduced the severity of infections caused by invasive P. aeruginosa in the 6-h-healing model. This result also coincided with significantly reduced bacterial colonization at 48 h. In vitro, human tear fluid significantly reduced the ability of invasive and cytotoxic bacteria to translocate across corneal epithelia and increased transepithelial resistance with or without bacterial inoculation. These data show that human tear fluid can protect against P. aeruginosa corneal infection in vivo and that the mechanism likely involves enhanced epithelial barrier function in addition to protection of individual epithelial cells against bacterial internalization and cytotoxicity.

* Corresponding author. Mailing address: School of Optometry, University of California, Berkeley, CA 94720-2020. Phone: (510) 643-0990. Fax: (510) 643-5109. E-mail: fleiszig{at}berkeley.edu

{triangledown} Published ahead of print on 26 February 2007.

Editor: V. J. DiRita

Infection and Immunity, May 2007, p. 2325-2332, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01404-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alarcon, I., Kwan, L., Yu, C., Evans, D. J., Fleiszig, S. M. J. (2009). Role of the Corneal Epithelial Basement Membrane in Ocular Defense against Pseudomonas aeruginosa. Infect. Immun. 77: 3264-3271 [Abstract] [Full Text]  


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