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 Porter, E.
Right arrow Articles by Quayle, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Porter, E.
Right arrow Articles by Quayle, A. J.

 Previous Article  |  Next Article 

Infection and Immunity, August 2005, p. 4823-4833, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4823-4833.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distinct Defensin Profiles in Neisseria gonorrhoeae and Chlamydia trachomatis Urethritis Reveal Novel Epithelial Cell-Neutrophil Interactions

Edith Porter,1,2* Huixia Yang,3,4 Sujata Yavagal,4 Gloria C. Preza,1 Omar Murillo,1 Heriberto Lima,1 Sheila Greene,3 Laily Mahoozi,4 Marcia Klein-Patel,5,6 Gill Diamond,5 Sunita Gulati,7 Tomas Ganz,2 Peter A. Rice,7 and Alison J. Quayle3,4

Department of Biological Sciences, California State University, Los Angeles, California 90032,1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095,2 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112,3 Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115,4 Department of Oral Biology, UMDNJ-New Jersey Dental School,5 UMDNJ-Graduate School of Biomedical Sciences, Newark, New Jersey 07103,6 Department of Infectious Diseases, Boston University Medical Center, Boston, Massachusetts 021187

Received 22 December 2004/ Returned for modification 22 February 2005/ Accepted 21 March 2005

Defensins are key participants in mucosal innate defense. The varied antimicrobial activity and differential distribution of defensins at mucosal sites indicate that peptide repertoires are tailored to site-specific innate defense requirements. Nonetheless, few studies have investigated changes in peptide profiles and function after in vivo pathogen challenge. Here, we determined defensin profiles in urethral secretions of healthy men and men with Chlamydia trachomatis- and Neisseria gonorrhoeae-mediated urethritis by immunoblotting for the epithelial defensins HBD1, HBD2, and HD5 and the neutrophil defensins HNP1 to -3 (HNP1-3). HBD1 was not detectable in secretions, and HBD2 was only induced in a small proportion of the urethritis patients; however, HD5 and HNP1-3 were increased in C. trachomatis infection and significantly elevated in N. gonorrhoeae infection. When HNP1-3 levels were low, HD5 appeared mostly as the propeptide; however, when HNP1-3 levels were >10 µg/ml, HD5 was proteolytically processed, suggesting neutrophil proteases might contribute to HD5 processing. HD5 and HNP1-3 were bactericidal against C. trachomatis and N. gonorrhoeae, but HD5 activity was dependent upon N-terminal processing of the peptide. In vitro proteolysis of proHD5 by neutrophil proteases and analysis of urethral secretions by surface-enhanced laser desorption ionization substantiated that neutrophils contribute the key convertases for proHD5 in the urethra during these infections. This contrasts with the small intestine, where Paneth cells secrete both proHD5 and its processing enzyme, trypsin. In conclusion, we describe a unique defensin expression repertoire in response to inflammatory sexually transmitted infections and a novel host defense mechanism wherein epithelial cells collaborate with neutrophils to establish an antimicrobial barrier during infection.

* Corresponding author. Mailing address: Department of Biological Sciences, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032. Phone: (323) 343-6353. Fax: (323) 343-6451. E-mail: eporter{at}calstatela.edu.

Editor: A. D. O'Brien

Infection and Immunity, August 2005, p. 4823-4833, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4823-4833.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wilson, C. L., Schmidt, A. P., Pirila, E., Valore, E. V., Ferri, N., Sorsa, T., Ganz, T., Parks, W. C. (2009). Differential Processing of {alpha}- and {beta}-Defensin Precursors by Matrix Metalloproteinase-7 (MMP-7). J. Biol. Chem. 284: 8301-8311 [Abstract] [Full Text]  
  • Dugan, A. S., Maginnis, M. S., Jordan, J. A., Gasparovic, M. L., Manley, K., Page, R., Williams, G., Porter, E., O'Hara, B. A., Atwood, W. J. (2008). Human {alpha}-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells. J. Biol. Chem. 283: 31125-31132 [Abstract] [Full Text]  
  • Do, T. Q., Moshkani, S., Castillo, P., Anunta, S., Pogosyan, A., Cheung, A., Marbois, B., Faull, K. F., Ernst, W., Chiang, S. M., Fujii, G., Clarke, C. F., Foster, K., Porter, E. (2008). Lipids Including Cholesteryl Linoleate and Cholesteryl Arachidonate Contribute to the Inherent Antibacterial Activity of Human Nasal Fluid. J. Immunol. 181: 4177-4187 [Abstract] [Full Text]  
  • Cunningham, K. A., Beagley, K. W. (2008). Male Genital Tract Chlamydial Infection: Implications for Pathology and Infertility. Biol. Reprod. 79: 180-189 [Abstract] [Full Text]  
  • Klotman, M. E., Rapista, A., Teleshova, N., Micsenyi, A., Jarvis, G. A., Lu, W., Porter, E., Chang, T. L. (2008). Neisseria gonorrhoeae-Induced Human Defensins 5 and 6 Increase HIV Infectivity: Role in Enhanced Transmission. J. Immunol. 180: 6176-6185 [Abstract] [Full Text]  
  • Mount, K. L. B., Townsend, C. A., Bauer, M. E. (2007). Haemophilus ducreyi Is Resistant to Human Antimicrobial Peptides. Antimicrob. Agents Chemother. 51: 3391-3393 [Abstract] [Full Text]  
  • Mitchell, G. B., Al-Haddawi, M. H., Clark, M. E., Beveridge, J. D., Caswell, J. L. (2007). Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells. Infect. Immun. 75: 1325-1334 [Abstract] [Full Text]  
  • Valore, E. V., Wiley, D. J., Ganz, T. (2006). Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis.. Infect. Immun. 74: 5693-5702 [Abstract] [Full Text]  
  • Buck, C. B., Day, P. M., Thompson, C. D., Lubkowski, J., Lu, W., Lowy, D. R., Schiller, J. T. (2006). Human {alpha}-defensins block papillomavirus infection. Proc. Natl. Acad. Sci. USA 103: 1516-1521 [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»