|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 26 October 2004
doi: 10.1242/jcs.01500
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
1 Epithelial Pathobiology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
2 Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, GA 30322, USA
3 Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
4 Department of Anatomy, University of Virginia, Charlottesville, Virginia 22908-0732, USA
* Author for correspondence (e-mail: agewirt{at}emory.edu)
Accepted 18 August 2004
Apical colonization of polarized epithelia by Salmonella typhimurium results in translocation of flagellin to the basolateral membrane domain, thus enabling activation of toll-like receptor 5 (TLR5)-mediated pro-inflammatory gene expression. Such flagellin transcytosis occurred without a change in epithelial permeability to 40 kDa FITC dextran, did not require bacterial motility and was independent of transepithelial movement of intact bacteria. Flagellin transcytosis was blocked at 20°C, suggesting dependence on vesicular transport consistent with results from confocal microscopy that showed flagellin independent of bacteria inside epithelial cells. Furthermore, vesicles isolated from S. typhimurium-infected epithelia were highly enriched in flagellin. Flagellin transcytosis was dependent upon genes of Salmonella pathogenicity island (SPI)-2, which alter vesicular trafficking, but independent of SPI-1 that mediates bacterial invasion. Furthermore, such SPI-2 mutants were unable to mediate the localization of flagellin into intracellular vesicles consistent with flagellin transcytosis mediated by a S. typhimurium take-over of host vesicle trafficking pathways. As a result of their inability to transcytose flagellin, apical colonization by SPI-2 mutants induced substantially less epithelial IL-8 secretion than wild-type strains suggesting that such SPI-2 mediated transcytosis of flagellin plays a role in the pathogenesis of the mucosal inflammation characteristic of human Salmonellosis.
Key words: Toll-like receptor 5 (TLR5), Inflammation, IL-8, Cell polarity
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  K.-i. Uchiya and T. Nikai Salmonella virulence factor SpiC is involved in expression of flagellin protein and mediates activation of the signal transduction pathways in macrophages Microbiology, November 1, 2008; 154(11): 3491 - 3502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Yoon and J. J. Mekalanos Decreased Potency of the Vibrio cholerae Sheathed Flagellum To Trigger Host Innate Immunity Infect. Immun., March 1, 2008; 76(3): 1282 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Sun, H. G. Rolan, and R. M. Tsolis Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium J. Biol. Chem., November 23, 2007; 282(47): 33897 - 33901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-i. Sano, Y. Takada, S. Goto, K. Maruyama, Y. Shindo, K. Oka, H. Matsui, and K. Matsuo Flagella Facilitate Escape of Salmonella from Oncotic Macrophages J. Bacteriol., November 15, 2007; 189(22): 8224 - 8232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Coburn, I. Sekirov, and B. B. Finlay Type III Secretion Systems and Disease Clin. Microbiol. Rev., October 1, 2007; 20(4): 535 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Badie, D. M. Heithoff, R. L. Sinsheimer, and M. J. Mahan Altered Levels of Salmonella DNA Adenine Methylase Are Associated with Defects in Gene Expression, Motility, Flagellar Synthesis, and Bile Resistance in the Pathogenic Strain 14028 but Not in the Laboratory Strain LT2 J. Bacteriol., March 1, 2007; 189(5): 1556 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. Steiner How Flagellin and Toll-Like Receptor 5 Contribute to Enteric Infection Infect. Immun., February 1, 2007; 75(2): 545 - 552. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Tobar, L. J. Carreno, S. M. Bueno, P. A. Gonzalez, J. E. Mora, S. A. Quezada, and A. M. Kalergis Virulent Salmonella enterica Serovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells. Infect. Immun., November 1, 2006; 74(11): 6438 - 6448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Gewirtz, M. Vijay-Kumar, S. R. Brant, R. H. Duerr, D. L. Nicolae, and J. H. Cho Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1157 - G1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rimoldi, M. Chieppa, P. Larghi, M. Vulcano, P. Allavena, and M. Rescigno Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different Blood, October 15, 2005; 106(8): 2818 - 2826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Coburn, Y. Li, D. Owen, B. A. Vallance, and B. B. Finlay Salmonella enterica Serovar Typhimurium Pathogenicity Island 2 Is Necessary for Complete Virulence in a Mouse Model of Infectious Enterocolitis Infect. Immun., June 1, 2005; 73(6): 3219 - 3227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mumy and B. A. McCormick Events at the Host-Microbial Interface of the Gastrointestinal Tract II. Role of the intestinal epithelium in pathogen-induced inflammation Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G854 - G859. [Abstract] [Full Text] [PDF]
|
|
