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 Ceponis, P. J. M.
Right arrow Articles by Sherman, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ceponis, P. J. M.
Right arrow Articles by Sherman, P. M.

 Previous Article  |  Next Article 

Infection and Immunity, March 2003, p. 1396-1404, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1396-1404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Enterohemorrhagic Escherichia coli O157:H7 Disrupts Stat1-Mediated Gamma Interferon Signal Transduction in Epithelial Cells

Peter J. M. Ceponis,1,2 Derek M. McKay,3 Joyce C. Y. Ching,1,4 Perpetual Pereira,1 and Philip M. Sherman1,2,4,5*

Research Institute, Hospital for Sick Children,1 Department of Laboratory Medicine & Pathobiology,2 Institute of Medical Science,4 Department of Paediatrics, University of Toronto, Toronto,5 Intestinal Disease Research Programme, McMaster University, Hamilton, Canada3

Received 22 April 2002/ Returned for modification 30 July 2002/ Accepted 13 November 2002

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a clinically important bacterial enteropathogen that manipulates a variety of host cell signal transduction cascades to establish infection. However, the effect of EHEC O157:H7 on Jak/Stat signaling is unknown. To define the effect of EHEC infection on epithelial gamma interferon (IFN-{gamma})-Stat1 signaling, human T84 and HEp-2 epithelial cells were infected with EHEC O157:H7 and then stimulated with recombinant human IFN-{gamma}. Cells were also infected with different EHEC strains, heat-killed EHEC, enteropathogenic E. coli (EPEC) O127:H6, and the commensal strain E. coli HB101. Nuclear and whole-cell protein extracts were prepared and were assayed by an electrophoretic mobility shift assay (EMSA) and by Western blotting, respectively. Cells were also processed for immunofluorescence to detect the subcellular localization of Stat1. The EMSA revealed inducible, but not constitutive, Stat1 activation upon IFN-{gamma} treatment of both cell lines. The EMSA also showed that 6 h of EHEC O157:H7 infection, but not 30 min of EHEC O157:H7 infection, prevented subsequent Stat1 DNA binding induced by IFN-{gamma}, whereas infection with EPEC did not. Immunoblotting showed that infection with EHEC, but not infection with EPEC, eliminated IFN-{gamma}-induced Stat1 tyrosine phosphorylation in both dose- and time-dependent fashions and disrupted inducible protein expression of the Stat1-dependent gene interferon regulatory factor 1. Immunofluorescence revealed that EHEC infection did not prevent nuclear accumulation of Stat1 after IFN-{gamma} treatment. Also, Stat1 tyrosine phosphorylation was suppressed by different EHEC isolates, including intimin-, type III secretion- and plasmid-deficient strains, but not by HB101 and heat-killed EHEC. These findings indicate the novel disruption of host cell signaling caused by EHEC infection but not by EPEC infection.

* Corresponding author. Mailing address: Rm. 8409, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Phone: (416) 813-7734. Fax: (416) 813-6531. E-mail: philip.sherman{at}sickkids.ca.

Editor: V. J. DiRita

Infection and Immunity, March 2003, p. 1396-1404, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1396-1404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bellmeyer, A., Cotton, C., Kanteti, R., Koutsouris, A., Viswanathan, V. K., Hecht, G. (2009). Enterohemorrhagic Escherichia coli suppresses inflammatory response to cytokines and its own toxin. Am. J. Physiol. Gastrointest. Liver Physiol. 297: G576-G581 [Abstract] [Full Text]  
  • Jandu, N., Zeng, Z. J., Johnson-Henry, K. C., Sherman, P. M. (2009). Probiotics prevent enterohaemorrhagic Escherichia coli O157 : H7-mediated inhibition of interferon-{gamma}-induced tyrosine phosphorylation of STAT-1. Microbiology 155: 531-540 [Abstract] [Full Text]  
  • Vareille, M., Rannou, F., Thelier, N., Glasser, A.-L., de Sablet, T., Martin, C., Gobert, A. P. (2008). Heme Oxygenase-1 Is a Critical Regulator of Nitric Oxide Production in Enterohemorrhagic Escherichia coli-Infected Human Enterocytes. J. Immunol. 180: 5720-5726 [Abstract] [Full Text]  
  • Reardon, C., McKay, D. M. (2007). TGF-beta Suppresses IFN-{gamma}-STAT1-Dependent Gene Transcription by Enhancing STAT1-PIAS1 Interactions in Epithelia but Not Monocytes/Macrophages. J. Immunol. 178: 4284-4295 [Abstract] [Full Text]  
  • Jandu, N., Ceponis, P. J. M., Kato, S., Riff, J. D., McKay, D. M., Sherman, P. M. (2006). Conditioned Medium from Enterohemorrhagic Escherichia coli-Infected T84 Cells Inhibits Signal Transducer and Activator of Transcription 1 Activation by Gamma Interferon. Infect. Immun. 74: 1809-1818 [Abstract] [Full Text]  
  • Riff, J. D., Callahan, J. W., Sherman, P. M. (2005). Cholesterol-Enriched Membrane Microdomains Are Required for Inducing Host Cell Cytoskeleton Rearrangements in Response to Attaching-Effacing Escherichia coli. Infect. Immun. 73: 7113-7125 [Abstract] [Full Text]  
  • Stekel, D. J., Sarti, D., Trevino, V., Zhang, L., Salmon, M., Buckley, C. D., Stevens, M., Pallen, M. J., Penn, C., Falciani, F. (2005). Analysis of host response to bacterial infection using error model based gene expression microarray experiments. Nucleic Acids Res 33: e53-e53 [Abstract] [Full Text]  
  • Viswanathan, V. K., Koutsouris, A., Lukic, S., Pilkinton, M., Simonovic, I., Simonovic, M., Hecht, G. (2004). Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function. Infect. Immun. 72: 3218-3227 [Abstract] [Full Text]  
  • Mitchell, D. J., Huynh, H. Q., Ceponis, P. J. M., Jones, N. L., Sherman, P. M. (2004). Helicobacter pylori Disrupts STAT1-Mediated Gamma Interferon-Induced Signal Transduction in Epithelial Cells. Infect. Immun. 72: 537-545 [Abstract] [Full Text]  
  • Ceponis, P. J. M., McKay, D. M., Menaker, R. J., Galindo-Mata, E., Jones, N. L. (2003). Helicobacter pylori Infection Interferes with Epithelial Stat6-Mediated Interleukin-4 Signal Transduction Independent of cagA, cagE, or VacA. J. Immunol. 171: 2035-2041 [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»