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Infect. Immun., Jun 1995, 2302-2309, Vol 63, No. 6
Copyright © 1995, American Society for Microbiology

Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis

BA McCormick, SI Miller, D Carnes and JL Madara
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Salmonella serotypes which elicit human enteritis cannot be distinguished from those that do not on the basis of their in vitro interactions with eukaryotic cells. We have recently reported that an enteritis-producing strain of Salmonella typhimurium signals intact intestinal epithelium to recruit subepithelial neutrophils to migrate across the epithelial (B. A. McCormick, S. P. Colgan, C. D. Archer, S. I. Miller, and J. L. Madara, J. Cell Biol. 123:895-907, 1993). We now utilize a cell culture model of human intestinal epithelium (with T84 cells) to examine whether such transepithelial signaling to neutrophils by salmonellae is predictive of potential to elicit gastroenteritis. Various Salmonella serotypes, including S. typhimurium, S. enteritidis, S. pullorum, S. arizonae, S. typhi, and S. paratyphi, as well as invasion-defective mutants of S. typhimurium, were studied. Strains or serotypes which elicit diffuse enteritis in humans (defined histologically as transepithelial migration of neutrophils) exhibited transepithelial signaling to neutorphils across epithelial cell monolayers, while those which do not elicit diffuse enteritis in humans did not display transepithelial signaling. In contrast, the ability to enter the apical surface of T84 cells did not differentiate strains or serotypes which induce diffuse enteritis from those which do not. These results strongly suggest that the ability of salmonellae to elicit transepithelial signaling to neutrophils is a key virulence mechanism underlying Salmonella-elicited enteritis.

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• Gewirtz, A. T., Siber, A. M., Madara, J. L., McCormick, B. A. (1999). Orchestration of Neutrophil Movement by Intestinal Epithelial Cells in Response to Salmonella typhimurium Can Be Uncoupled from Bacterial Internalization. Infect. Immun. 67: 608-617 [Abstract] [Full Text]  
• Eaves-Pyles, T., Szabo, C., Salzman, A. L. (1999). Bacterial Invasion Is Not Required for Activation of NF-kappa B in Enterocytes. Infect. Immun. 67: 800-804 [Abstract] [Full Text]  
• Jones, M. A., Wood, M. W., Mullan, P. B., Watson, P. R., Wallis, T. S., Galyov, E. E. (1998). Secreted Effector Proteins of Salmonella dublin Act in Concert To Induce Enteritis. Infect. Immun. 66: 5799-5804 [Abstract] [Full Text]  
• Baumler, A. J., Tsolis, R. M., Ficht, T. A., Adams, L. G. (1998). Evolution of Host Adaptation in Salmonella enterica. Infect. Immun. 66: 4579-4587 [Full Text]  
• Hueck, C. J. (1998). Type III Protein Secretion Systems in Bacterial Pathogens of Animals and Plants. Microbiol. Mol. Biol. Rev. 62: 379-433 [Abstract] [Full Text]  
• Weinstein, D. L., O'Neill, B. L., Hone, D. M., Metcalf, E. S. (1998). Differential Early Interactions between Salmonella enterica Serovar Typhi and Two Other Pathogenic Salmonella Serovars with Intestinal Epithelial Cells. Infect. Immun. 66: 2310-2318 [Abstract] [Full Text]  
• Watson, P. R., Galyov, E. E., Paulin, S. M., Jones, P. W., Wallis, T. S. (1998). Mutation of invH, but Not stn, Reduces Salmonella-Induced Enteritis in Cattle. Infect. Immun. 66: 1432-1438 [Abstract] [Full Text]  
• McCormick, B. A., Parkos, C. A., Colgan, S. P., Carnes, D. K., Madara, J. L. (1998). Apical Secretion of a Pathogen-Elicited Epithelial Chemoattractant Activity in Response to Surface Colonization of Intestinal Epithelia by Salmonella typhimurium. J. Immunol. 160: 455-466 [Abstract] [Full Text]