This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zaidi, T. S.
Right arrow Articles by Pier, G. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zaidi, T. S.
Right arrow Articles by Pier, G. B.

 Previous Article  |  Next Article 

Infection and Immunity, March 1999, p. 1481-1492, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cystic Fibrosis Transmembrane Conductance Regulator-Mediated Corneal Epithelial Cell Ingestion of Pseudomonas aeruginosa Is a Key Component in the Pathogenesis of Experimental Murine Keratitis

Tanweer S. Zaidi, Jeffrey Lyczak, Michael Preston, and Gerald B. Pier*

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115-5804

Received 30 September 1998/Returned for modification 18 November 1998/Accepted 4 December 1998

Previous findings indicate that the cystic fibrosis transmembrane conductance regulator (CFTR) is a ligand for Pseudomonas aeruginosa ingestion into respiratory epithelial cells. In experimental murine keratitis, P. aeruginosa enters corneal epithelial cells. We determined the importance of CFTR-mediated uptake of P. aeruginosa by corneal cells in experimental eye infections. Entry of noncytotoxic (exoU) P. aeruginosa into human and rabbit corneal cell cultures was inhibited with monoclonal antibodies and peptides specific to CFTR amino acids 108 to 117. Immunofluorescence microscopy and flow cytometry demonstrated CFTR in the intact murine corneal epithelium, and electron microscopy showed that CFTR binds to P. aeruginosa following corneal cell ingestion. In experimental murine eye infections, multiple additions of 5 nM CFTR peptide 103-117 to inocula of either cytotoxic (exoU+) or noncytotoxic P. aeruginosa resulted in large reductions in bacteria in the eye and markedly lessened eye pathology. Compared with wild-type C57BL/6 mice, heterozygous Delta F508 Cftr mice infected with P. aeruginosa had an approximately 10-fold reduction in bacterial levels in the eye and consequent reductions in eye pathology. Homozygous Delta F508 Cftr mice were nearly completely resistant to P. aeruginosa corneal infection. CFTR-mediated internalization of P. aeruginosa by buried corneal epithelial cells is critical to the pathogenesis of experimental eye infection, while in the lung, P. aeruginosa uptake by surface epithelial cells enhances P. aeruginosa clearance from this tissue.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115-5804. Phone: (617) 525-2269; Fax: (617) 731-1541. E-mail: gpier{at}channing.harvard.edu.

Infection and Immunity, March 1999, p. 1481-1492, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Alarcon, I., Evans, D. J., Fleiszig, S. M. J. (2009). The Role of Twitching Motility in Pseudomonas aeruginosa Exit from and Translocation of Corneal Epithelial Cells. IOVS 50: 2237-2244 [Abstract] [Full Text]  
  • Kukavica-Ibrulj, I, Levesque, R C (2008). Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies. Lab Anim 42: 389-412 [Abstract] [Full Text]  
  • Zaidi, T., Bajmoczi, M., Zaidi, T., Golan, D. E., Pier, G. B. (2008). Disruption of CFTR-Dependent Lipid Rafts Reduces Bacterial Levels and Corneal Disease in a Murine Model of Pseudomonas aeruginosa Keratitis. IOVS 49: 1000-1009 [Abstract] [Full Text]  
  • DiGiandomenico, A., Rao, J., Harcher, K., Zaidi, T. S., Gardner, J., Neely, A. N., Pier, G. B., Goldberg, J. B. (2007). Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc. Natl. Acad. Sci. USA 104: 4624-4629 [Abstract] [Full Text]  
  • Yamamoto, N., Yamamoto, N., Petroll, M. W., Jester, J. V., Cavanagh, H. D. (2006). Regulation of Pseudomonas aeruginosa Internalization after Contact Lens Wear In Vivo and in Serum-Free Culture by Ocular Surface Cells.. IOVS 47: 3430-3440 [Abstract] [Full Text]  
  • Zolfaghar, I., Evans, D. J., Ronaghi, R., Fleiszig, S. M. J. (2006). Type III Secretion-Dependent Modulation of Innate Immunity as One of Multiple Factors Regulated by Pseudomonas aeruginosa RetS. Infect. Immun. 74: 3880-3889 [Abstract] [Full Text]  
  • Zaidi, T. S., Priebe, G. P., Pier, G. B. (2006). A Live-Attenuated Pseudomonas aeruginosa Vaccine Elicits Outer Membrane Protein-Specific Active and Passive Protection against Corneal Infection. Infect. Immun. 74: 975-983 [Abstract] [Full Text]  
  • Blais, D. R., Vascotto, S. G., Griffith, M., Altosaar, I. (2005). LBP and CD14 Secreted in Tears by the Lacrimal Glands Modulate the LPS Response of Corneal Epithelial Cells. IOVS 46: 4235-4244 [Abstract] [Full Text]  
  • Yamamoto, N., Yamamoto, N., Petroll, M. W., Cavanagh, H. D., Jester, J. V. (2005). Internalization of Pseudomonas aeruginosa Is Mediated by Lipid Rafts in Contact Lens-Wearing Rabbit and Cultured Human Corneal Epithelial Cells. IOVS 46: 1348-1355 [Abstract] [Full Text]  
  • Zaidi, T., Mowrey-Mckee, M., Pier, G. B. (2004). Hypoxia Increases Corneal Cell Expression of CFTR Leading to Increased Pseudomonas aeruginosa Binding, Internalization, and Initiation of Inflammation. IOVS 45: 4066-4074 [Abstract] [Full Text]  
  • Xu, X.-F., Tan, Y.-W., Lam, L., Hackett, J., Zhang, M., Mok, Y.-K. (2004). NMR Structure of a Type IVb Pilin from Salmonella typhi and Its Assembly into Pilus. J. Biol. Chem. 279: 31599-31605 [Abstract] [Full Text]  
  • Priebe, G. P., Dean, C. R., Zaidi, T., Meluleni, G. J., Coleman, F. T., Coutinho, Y. S., Noto, M. J., Urban, T. A., Pier, G. B., Goldberg, J. B. (2004). The galU Gene of Pseudomonas aeruginosa Is Required for Corneal Infection and Efficient Systemic Spread following Pneumonia but Not for Infection Confined to the Lung. Infect. Immun. 72: 4224-4232 [Abstract] [Full Text]  
  • Lyczak, J. B. (2003). Commensal Bacteria Increase Invasion of Intestinal Epithelium by Salmonella enterica Serovar Typhi. Infect. Immun. 71: 6610-6614 [Abstract] [Full Text]  
  • Cannon, C. L., Kowalski, M. P., Stopak, K. S., Pier, G. B. (2003). Pseudomonas aeruginosa-Induced Apoptosis Is Defective in Respiratory Epithelial Cells Expressing Mutant Cystic Fibrosis Transmembrane Conductance Regulator. Am. J. Respir. Cell Mol. Bio. 29: 188-197 [Abstract] [Full Text]  
  • Ajonuma, L. C., Chan, L. N., Ng, E. H. Y., Chow, P. H., Kung, L. S., Cheung, A. N. Y., Briton-Jones, C., Lok, I. H., Haines, C. J., Chan, H. C. (2003). Characterization of epithelial cell culture from human hydrosalpinges and effects of its conditioned medium on embryo development and sperm motility. Hum Reprod 18: 291-298 [Abstract] [Full Text]  
  • Lyczak, J. B., Pier, G. B. (2002). Salmonella enterica Serovar Typhi Modulates Cell Surface Expression of Its Receptor, the Cystic Fibrosis Transmembrane Conductance Regulator, on the Intestinal Epithelium. Infect. Immun. 70: 6416-6423 [Abstract] [Full Text]  
  • Swords, W. E., Chance, D. L., Cohn, L. A., Shao, J., Apicella, M. A., Smith, A. L. (2002). Acylation of the Lipooligosaccharide of Haemophilus influenzae and Colonization: an htrB Mutation Diminishes the Colonization of Human Airway Epithelial Cells. Infect. Immun. 70: 4661-4668 [Abstract] [Full Text]  
  • Schroeder, T. H., Lee, M. M., Yacono, P. W., Cannon, C. L., Gerceker, A. A., Golan, D. E., Pier, G. B. (2002). CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-kappa B translocation. Proc. Natl. Acad. Sci. USA 99: 6907-6912 [Abstract] [Full Text]  
  • Priebe, G. P., Brinig, M. M., Hatano, K., Grout, M., Coleman, F. T., Pier, G. B., Goldberg, J. B. (2002). Construction and Characterization of a Live, Attenuated aroA Deletion Mutant of Pseudomonas aeruginosa as a Candidate Intranasal Vaccine. Infect. Immun. 70: 1507-1517 [Abstract] [Full Text]  
  • Al-Nakkash, L., Reinach, P. S. (2001). Activation of a CFTR-Mediated Chloride Current in a Rabbit Corneal Epithelial Cell Line. IOVS 42: 2364-2370 [Abstract] [Full Text]  
  • Fleiszig, S. M. J., Arora, S. K., Van, R., Ramphal, R. (2001). FlhA, a Component of the Flagellum Assembly Apparatus of Pseudomonas aeruginosa, Plays a Role in Internalization by Corneal Epithelial Cells. Infect. Immun. 69: 4931-4937 [Abstract] [Full Text]  
  • Schroeder, T. H., Reiniger, N., Meluleni, G., Grout, M., Coleman, F. T., Pier, G. B. (2001). Transgenic Cystic Fibrosis Mice Exhibit Reduced Early Clearance of Pseudomonas aeruginosa from the Respiratory Tract. J. Immunol. 166: 7410-7418 [Abstract] [Full Text]  
  • Plotnikova, J. M., Rahme, L. G., Ausubel, F. M. (2000). Pathogenesis of the Human Opportunistic Pathogen Pseudomonas aeruginosa PA14 in Arabidopsis. Plant Physiol. 124: 1766-1774 [Abstract] [Full Text]  
  • Chroneos, Z. C., Wert, S. E., Livingston, J. L., Hassett, D. J., Whitsett, J. A. (2000). Role of Cystic Fibrosis Transmembrane Conductance Regulator in Pulmonary Clearance of Pseudomonas aeruginosa In Vivo. J. Immunol. 165: 3941-3950 [Abstract] [Full Text]  
  • Pier, G. B. (2000). Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. Proc. Natl. Acad. Sci. USA 97: 8822-8828 [Abstract] [Full Text]  
  • Gerceker, A. A., Zaidi, T., Marks, P., Golan, D. E., Pier, G. B. (2000). Impact of Heterogeneity within Cultured Cells on Bacterial Invasion: Analysis of Pseudomonas aeruginosa and Salmonella enterica Serovar Typhi Entry into MDCK cells by Using a Green Fluorescent Protein-Labelled Cystic Fibrosis Transmembrane Conductance Regulator Receptor. Infect. Immun. 68: 861-870 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»