This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00721-06v1 74/11/6075    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guttman, J. A. Articles by Finlay, B. B. Search for Related Content PubMed PubMed Citation Articles by Guttman, J. A. Articles by Finlay, B. B.

 Previous Article  |  Next Article 

Infection and Immunity, November 2006, p. 6075-6084, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00721-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Evidence that Tight Junctions Are Disrupted Due to Intimate Bacterial Contact and Not Inflammation during Attaching and Effacing Pathogen Infection In Vivo

The University of British Columbia, Michael Smith Laboratories, 301-2185 East Mall, Vancouver, BC, Canada V6T 1Z4,¹ The University of British Columbia, Department of Cellular and Physiological Sciences, Division of Anatomy and Cell Biology, Life Sciences Centre, 3.401-2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3²

Received 4 May 2006/ Returned for modification 10 August 2006/ Accepted 18 August 2006

It is widely accepted that tight junctions are altered during infections by attaching and effacing (A/E) pathogens. These disruptions have been demonstrated both in vitro and more recently in vivo. For in vivo experiments, the murine model of A/E infection with Citrobacter rodentium is the animal model of choice. In addition to effects on tight junctions, these bacteria also colonize the colon at high levels, efface colonocyte microvilli, and cause hyperplasia and inflammation. Although we have recently demonstrated that tight junctions are disrupted by C. rodentium, the issue of direct effects of bacteria on epithelial cell junctions versus the indirect effects of inflammation still remains to be clarified. Here, we demonstrate that during the C. rodentium infections, inflammation plays no discernible role in the alteration of tight junctions. The distribution of the tight junction proteins, claudin-1, -3, and -5, are unaffected in inflamed colon, and junctions appear morphologically unaltered when viewed by electron microscopy. Additionally, tracer molecules are not capable of penetrating the inflamed colonic epithelium of infected mice that have cleared the bacteria. Finally, infected colonocytes from mice exposed to C. rodentium for 14 days, which have high levels of bacterial attachment to colonocytes as well as inflammation, have characteristic, altered claudin localization whereas cells adjacent to infected colonocytes retain their normal claudin distribution. We conclude that inflammation plays no discernible role in tight junction alteration during A/E pathogenesis and that tight junction disruption in vivo appears dependent only on the direct intimate attachment of the pathogenic bacteria to the cells.

Published ahead of print on 5 September 2006.

Editor: A. D. O'Brien

This article has been cited by other articles:

• Soong, G., Parker, D., Magargee, M., Prince, A. S. (2008). The Type III Toxins of Pseudomonas aeruginosa Disrupt Epithelial Barrier Function. J. Bacteriol. 190: 2814-2821 [Abstract] [Full Text]  
• Bergstrom, K. S. B., Guttman, J. A., Rumi, M., Ma, C., Bouzari, S., Khan, M. A., Gibson, D. L., Vogl, A. W., Vallance, B. A. (2008). Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen. Infect. Immun. 76: 796-811 [Abstract] [Full Text]  
• Alto, N. M., Weflen, A. W., Rardin, M. J., Yarar, D., Lazar, C. S., Tonikian, R., Koller, A., Taylor, S. S., Boone, C., Sidhu, S. S., Schmid, S. L., Hecht, G. A., Dixon, J. E. (2007). The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. JCB 178: 1265-1278 [Abstract] [Full Text]  
• Shaykhiev, R., Bals, R. (2007). Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis. J. Leukoc. Biol. 82: 1-15 [Abstract] [Full Text]