This Article Full Text Full Text (PDF) Supplemental material 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 Ingersoll, M. A. Articles by Zychlinsky, A. Search for Related Content PubMed PubMed Citation Articles by Ingersoll, M. A. Articles by Zychlinsky, A.

ShiA Abrogates the Innate T-Cell Response to Shigella flexneri Infection

Molly A. Ingersoll^1,2, and Arturo Zychlinsky^1*

Max Planck Institute for Infection Biology, 21/22 Schumannstraße, 10117 Berlin, Germany,¹ Skirball Institute and Department of Microbiology, New York University Medical Center, 540 First Avenue, New York, New York 10016²

Received 21 October 2005/ Returned for modification 5 December 2005/ Accepted 18 January 2006

Shigella spp. are the causative agent of bacillary dysentery. Infection results in acute colonic injury due to the host inflammatory response. The mediators of the damage, infiltrating polymorphonuclear leukocytes (PMN), also resolve the infection. Shigella flexneri's virulence effectors are encoded on its large virulence plasmid and on pathogenicity islands in the chromosome. The SHI-2 pathogenicity island encodes the virulence factor ShiA, which down-regulates Shigella-induced inflammation. In the rabbit ileal loop model, infection with a shiA null strain (shiA) induces a more severe inflammation than wild-type infection. Conversely, a Shigella strain that overexpresses ShiA (ShiA⁺) is less inflammatory than the wild-type strain. To determine the host responses modulated by ShiA, we performed infection studies using the mouse lung model, which recapitulates the phenotypes observed in the rabbit ileal loop model. Significantly, ShiA⁺ strain-infected mice cleared the bacteria and survived infection, while wild-type- and shiA strain-infected mice could not clear the bacteria and ultimately died. Surprisingly, microarray analysis of infected lungs revealed the regulation of genes involved in innate T-cell responses to infection. Immunohistochemistry showed that wild-type- and shiA strain-infected animals have greater numbers of PMN and T cells in their lungs over the course of infection than ShiA⁺ strain-infected animals. These results suggest that the T-cell innate response is suppressed by ShiA in Shigella infections.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. B. Bliska

Present address: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.

This article has been cited by other articles:

• Schroeder, G. N., Hilbi, H. (2008). Molecular Pathogenesis of Shigella spp.: Controlling Host Cell Signaling, Invasion, and Death by Type III Secretion. Clin. Microbiol. Rev. 21: 134-156 [Abstract] [Full Text]  
• Shim, D.-H., Suzuki, T., Chang, S.-Y., Park, S.-M., Sansonetti, P. J., Sasakawa, C., Kweon, M.-N. (2007). New Animal Model of Shigellosis in the Guinea Pig: Its Usefulness for Protective Efficacy Studies. J. Immunol. 178: 2476-2482 [Abstract] [Full Text]