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 Fox, J. G.
Right arrow Articles by Erdman, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fox, J. G.
Right arrow Articles by Erdman, S. E.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Medline Plus Health Information
*Gastroenteritis

 Previous Article  |  Next Article 

Infection and Immunity, February 2004, p. 1116-1125, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.1116-1125.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Gastroenteritis in NF-{kappa}B-Deficient Mice Is Produced with Wild-Type Camplyobacter jejuni but Not with C. jejuni Lacking Cytolethal Distending Toxin despite Persistent Colonization with Both Strains

James G. Fox,1* Arlin B. Rogers,1 Mark T. Whary,1 Zhongming Ge,1 Nancy S. Taylor,1 Sandy Xu,1 Bruce H. Horwitz,2 and Susan E. Erdman1

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts,1 Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts2

Received 24 April 2002/ Returned for modification 11 September 2003/ Accepted 21 October 2003

Campylobacter jejuni continues to be a leading cause of bacterial enteritis in humans. However, because there are no readily available animal models to study the pathogenesis of C. jejuni-related diseases, the significance of potential virulence factors, such as cytolethal distending toxin (CDT), in vivo are poorly understood. Mice deficient in NF-{kappa}B subunits (p50-/- p65+/-) in a C57BL/129 background are particularly susceptible to colitis induced by another enterohepatic microaerobe, Helicobacter hepaticus, which, like C. jejuni, produces CDT. Wild-type C. jejuni 81-176 and an isogenic mutant lacking CDT activity (cdtB mutant) were inoculated into NF-{kappa}B-deficient (3X) and C57BL/129 mice. Wild-type C. jejuni colonized 29 and 50% of the C57BL/129 mice at 2 and 4 months postinfection (p.i.), respectively, whereas the C. jejuni cdtB mutant colonized 50% of the C57BL/129 mice at 2 p.i. but none of the mice at 4 months p.i. Although the C57BL/129 mice developed mild gastritis and typhlocolitis, they had robust immunoglobulin G (IgG) and Th1-promoted IgG2a humoral responses to both the wild-type strain and the C. jejuni cdtB mutant. In contrast, 75 to 100% of the 3X mice were colonized with both the wild type and the C. jejuni cdtB mutant at similar levels at all times examined. Wild-type C. jejuni caused moderately severe gastritis and proximal duodenitis in 3X mice that were more severe than the gastrointestinal lesions caused by the C. jejuni cdtB mutant. Persistent colonization of NF-{kappa}B-deficient mice with the wild type and the C. jejuni cdtB mutant was associated with significantly impaired IgG and IgG2a humoral responses (P < 0.001), which is consistent with an innate or adaptive immune system defect(s). These results suggest that the mechanism of clearance of C. jejuni is NF-{kappa}B dependent and that CDT may have proinflammatory activity in vivo, as well as a potential role in the ability of C. jejuni to escape immune surveillance. NF-{kappa}B-deficient mice should be a useful model to further study the role of CDT and other aspects of C. jejuni pathogenesis.

* Corresponding author. Mailing address: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg. 16-825C, Cambridge, MA 02139. Phone: (617) 253-1735. Fax: (617) 252-1877. E-mail: jgfox{at}mit.edu.

Editor: V. J. DiRita

Infection and Immunity, February 2004, p. 1116-1125, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.1116-1125.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shen, Z., Feng, Y., Rogers, A. B., Rickman, B., Whary, M. T., Xu, S., Clapp, K. M., Boutin, S. R., Fox, J. G. (2009). Cytolethal Distending Toxin Promotes Helicobacter cinaedi-Associated Typhlocolitis in Interleukin-10-Deficient Mice. Infect. Immun. 77: 2508-2516 [Abstract] [Full Text]  
  • Rathinam, V. A. K., Appledorn, D. M., Hoag, K. A., Amalfitano, A., Mansfield, L. S. (2009). Campylobacter jejuni-Induced Activation of Dendritic Cells Involves Cooperative Signaling through Toll-Like Receptor 4 (TLR4)-MyD88 and TLR4-TRIF Axes. Infect. Immun. 77: 2499-2507 [Abstract] [Full Text]  
  • Toth, I., Nougayrede, J.-P., Dobrindt, U., Ledger, T. N., Boury, M., Morabito, S., Fujiwara, T., Sugai, M., Hacker, J., Oswald, E. (2009). Cytolethal Distending Toxin Type I and Type IV Genes Are Framed with Lambdoid Prophage Genes in Extraintestinal Pathogenic Escherichia coli. Infect. Immun. 77: 492-500 [Abstract] [Full Text]  
  • Al-Banna, N., Raghupathy, R., Albert, M. J. (2008). Correlation of Proinflammatory and Anti-Inflammatory Cytokine Levels with Histopathological Changes in an Adult Mouse Lung Model of Campylobacter jejuni Infection. CVI 15: 1780-1787 [Abstract] [Full Text]  
  • Zheng, J., Meng, J., Zhao, S., Singh, R., Song, W. (2008). Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells Requires Campylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-{kappa}B. Infect. Immun. 76: 4498-4508 [Abstract] [Full Text]  
  • Janssen, R., Krogfelt, K. A., Cawthraw, S. A., van Pelt, W., Wagenaar, J. A., Owen, R. J. (2008). Host-Pathogen Interactions in Campylobacter Infections: the Host Perspective. Clin. Microbiol. Rev. 21: 505-518 [Abstract] [Full Text]  
  • Sterzenbach, T., Lee, S. K., Brenneke, B., von Goetz, F., Schauer, D. B., Fox, J. G., Suerbaum, S., Josenhans, C. (2007). Inhibitory Effect of Enterohepatic Helicobacter hepaticus on Innate Immune Responses of Mouse Intestinal Epithelial Cells. Infect. Immun. 75: 2717-2728 [Abstract] [Full Text]  
  • Watson, R. O., Novik, V., Hofreuter, D., Lara-Tejero, M., Galan, J. E. (2007). A MyD88-Deficient Mouse Model Reveals a Role for Nramp1 in Campylobacter jejuni Infection. Infect. Immun. 75: 1994-2003 [Abstract] [Full Text]  
  • Mansfield, L. S., Bell, J. A., Wilson, D. L., Murphy, A. J., Elsheikha, H. M., Rathinam, V. A. K., Fierro, B. R., Linz, J. E., Young, V. B. (2007). C57BL/6 and Congenic Interleukin-10-Deficient Mice Can Serve as Models of Campylobacter jejuni Colonization and Enteritis. Infect. Immun. 75: 1099-1115 [Abstract] [Full Text]  
  • Chen, M. L., Ge, Z., Fox, J. G., Schauer, D. B. (2006). Disruption of Tight Junctions and Induction of Proinflammatory Cytokine Responses in Colonic Epithelial Cells by Campylobacter jejuni. Infect. Immun. 74: 6581-6589 [Abstract] [Full Text]  
  • Chang, C., Miller, J. F. (2006). Campylobacter jejuni Colonization of Mice with Limited Enteric Flora. Infect. Immun. 74: 5261-5271 [Abstract] [Full Text]  
  • Pratt, J. S., Sachen, K. L., Wood, H. D., Eaton, K. A., Young, V. B. (2006). Modulation of Host Immune Responses by the Cytolethal Distending Toxin of Helicobacter hepaticus.. Infect. Immun. 74: 4496-4504 [Abstract] [Full Text]  
  • Maurer, K. J., Rogers, A. B., Ge, Z., Wiese, A. J., Carey, M. C., Fox, J. G. (2006). Helicobacter pylori and cholesterol gallstone formation in C57L/J mice: a prospective study. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G175-G182 [Abstract] [Full Text]  
  • Ge, Z., Feng, Y., Whary, M. T., Nambiar, P. R., Xu, S., Ng, V., Taylor, N. S., Fox, J. G. (2005). Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice. Infect. Immun. 73: 3559-3567 [Abstract] [Full Text]  
  • Smith, C. K., Kaiser, P., Rothwell, L., Humphrey, T., Barrow, P. A., Jones, M. A. (2005). Campylobacter jejuni-Induced Cytokine Responses in Avian Cells. Infect. Immun. 73: 2094-2100 [Abstract] [Full Text]  
  • Stintzi, A., Marlow, D., Palyada, K., Naikare, H., Panciera, R., Whitworth, L., Clarke, C. (2005). Use of Genome-Wide Expression Profiling and Mutagenesis To Study the Intestinal Lifestyle of Campylobacter jejuni. Infect. Immun. 73: 1797-1810 [Abstract] [Full Text]  
  • Heywood, W., Henderson, B., Nair, S. P (2005). Cytolethal distending toxin: creating a gap in the cell cycle. J Med Microbiol 54: 207-216 [Abstract] [Full Text]  
  • Dassanayake, R. P., Zhou, Y., Hinkley, S., Stryker, C. J., Plauche, G., Borda, J. T., Sestak, K., Duhamel, G. E. (2005). Characterization of Cytolethal Distending Toxin of Campylobacter Species Isolated from Captive Macaque Monkeys. J. Clin. Microbiol. 43: 641-649 [Abstract] [Full Text]  
  • Boutin, S. R., Rogers, A. B., Zeli Shen, , Fry, R. C., Love, J. A., Nambiar, P. R., Suerbaum, S., Fox, J. G. (2004). Hepatic Temporal Gene Expression Profiling in Helicobacter hepaticus-Infected A/JCr Mice. Toxicol Pathol 32: 678-693 [Abstract]  


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