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 Russo, T. A.
Right arrow Articles by Murphy, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Russo, T. A.
Right arrow Articles by Murphy, P. M.

 Previous Article  |  Next Article 

Infection and Immunity, November 2003, p. 6435-6445, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6435-6445.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Neutrophil Chemotaxis Is Modulated by Capsule and O Antigen from an Extraintestinal Pathogenic Escherichia coli Strain

Thomas A. Russo,1,2,3,4* Bruce A. Davidson,3,5 Diana M. Topolnycky,1,3 Ruth Olson,1,3 Stacy A. Morrill,1,3 Paul R. Knight III,3,5 and Philip M. Murphy6

Department of Medicine,1 Department of Microbiology,2 The Witebsky Center for Microbial Pathogenesis,3 Veterans Administration Western New York Healthcare System,4 Department of Anesthesiology, University at Buffalo, Buffalo, New York 14214,5 Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208926

Received 19 May 2003/ Returned for modification 16 July 2003/ Accepted 18 August 2003

Gram-negative enteric bacilli, such as Escherichia coli, are common causes of nosocomial pneumonia. The interaction between pulmonary neutrophils and the infecting pathogen is a critical step in determining the outcome. Previous studies from our laboratory, for which a rat model of pneumonia was used, established that pulmonary neutrophil recruitment was modulated by the E. coli virulence factors capsule and O-specific antigen. To begin to understand the mechanism by which this recruitment occurs, we conducted in vitro and ex vivo chemotaxis assays, for which we used a clinically relevant E. coli isolate (CP9) and isogenic derivatives that were deficient in only the O antigen (CP921) or capsule (CP9.137) as chemoattractants with or without the high-affinity N-formylmethionyl-leucyl-phenylalanine receptor antagonist N-tert-butoxycarbonyl-methionine-leucine-phenylalanine (N-t-BOC). Given that only live E. coli was used for the initial in vitro chemotaxis assays, it was predicted that only N-t-BOC-sensitive chemotaxis would occur. However, both N-t-BOC-sensitive and -insensitive chemotaxis was observed. N-t-BOC-insensitive chemotaxis was mediated in part by interleukin 8, which was produced by neutrophils that had migrated toward E. coli. N-t-BOC-insensitive chemotaxis was only observed when live E. coli bacteria, not cell-free E. coli culture supernatants, were used as chemoattractants, suggesting that a direct E. coli-neutrophil interaction was necessary. The presence of both capsule and O antigen diminished total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis in vitro. The presence of capsule significantly decreased total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis ex vivo when cell-free bronchoalveolar lavage fluid from infected rats was used as the source of chemotactic factors. These effects of E. coli capsule and O antigen on neutrophil chemotaxis are novel, and they expand our understanding of the mechanisms by which these virulence traits contribute to the pathogenesis of gram-negative pneumonia and other extraintestinal infections.


* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, 3435 Main St., Biomedical Research Building, Room 141, Buffalo, NY 14214. Phone: (716) 829-2674. Fax: (716) 829-3889. E-mail: trusso{at}acsu.buffalo.edu.


Infection and Immunity, November 2003, p. 6435-6445, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6435-6445.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Nazareth, H., Genagon, S. A., Russo, T. A. (2007). Extraintestinal Pathogenic Escherichia coli Survives within Neutrophils. Infect. Immun. 75: 2776-2785 [Abstract] [Full Text]  
  • Russo, T. A., Davidson, B. A., Genagon, S. A., Warholic, N. M., MacDonald, U., Pawlicki, P. D., Beanan, J. M., Olson, R., Holm, B. A., Knight, P. R III (2005). E. coli virulence factor hemolysin induces neutrophil apoptosis and necrosis/lysis in vitro and necrosis/lysis and lung injury in a rat pneumonia model. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L207-L216 [Abstract] [Full Text]  
  • Singer, M., Sansonetti, P. J. (2004). IL-8 Is a Key Chemokine Regulating Neutrophil Recruitment in a New Mouse Model of Shigella-Induced Colitis. J. Immunol. 173: 4197-4206 [Abstract] [Full Text]