This Article Full Text Full Text (PDF) 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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raffatellu, M. Articles by Bäumler, A. J. Search for Related Content PubMed PubMed Citation Articles by Raffatellu, M. Articles by Bäumler, A. J.

The Vi Capsular Antigen of Salmonella enterica Serotype Typhi Reduces Toll-Like Receptor-Dependent Interleukin-8 Expression in the Intestinal Mucosa

Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center, 407 Reynolds Medical Building, College Station, Texas 77843-1114,¹ Dipartimento Scienze Biomediche, University of Sassari, Viale San Pietro 43/b, 07100 SASSARI, Italy,² Scott & White Clinic, College Station, Texas³

Received 11 January 2005/ Returned for modification 29 January 2005/ Accepted 5 February 2005

Human infections with nontyphoidal Salmonella serotypes, such as S. enterica serotype Typhimurium, are characterized by a massive neutrophil influx in the colon and terminal ileum. In contrast, neutrophils are scarce in intestinal infiltrates of typhoid fever patients. Here, we show that in S. enterica serotype Typhi, the causative agent of typhoid fever, expression of the Vi capsular antigen reduced expression of the neutrophil chemoattractant interleukin-8 (IL-8) in host cells. Capsulated bacteria elicited IL-8 expression in polarized human epithelial cells (T84) and human macrophage-like cells (THP-1) in vitro at significantly reduced levels compared to noncapsulated bacteria. Experiments with a human cell line (HEK293) transfected with human Toll-like receptors (TLRs) demonstrated that in the presence of TLR5 or TLR4/MD2/CD14, a noncapsulated serotype Typhi mutant was able to induce the expression of IL-8, while this host response was significantly reduced when cells were infected with the capsulated serotype Typhi wild type. The relevance of these in vitro observations for the interaction of serotype Typhi with its human host was further studied ex vivo using human colonic tissue explants. Expression of IL-8 was detected in human colonic tissue explants infected with serotype Typhimurium or a noncapsulated serotype Typhi mutant. In contrast, infection with the serotype Typhi wild type did not elicit IL-8 expression in colonic tissue explants. Collectively, these data suggest that the scarcity of neutrophils in intestinal infiltrates of typhoid fever patients is due to a capsule-mediated reduction of TLR-dependent IL-8 production in the intestinal mucosa.

Editor: J. T. Barbieri

This article has been cited by other articles:

• Munford, R. S. (2008). Sensing Gram-Negative Bacterial Lipopolysaccharides: a Human Disease Determinant?. Infect. Immun. 76: 454-465 [Full Text]  
• Sun, Y.-H., Rolan, H. G., Tsolis, R. M. (2007). Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium. J. Biol. Chem. 282: 33897-33901 [Abstract] [Full Text]  
• Forest, C., Faucher, S. P., Poirier, K., Houle, S., Dozois, C. M., Daigle, F. (2007). Contribution of the stg Fimbrial Operon of Salmonella enterica Serovar Typhi during Interaction with Human Cells. Infect. Immun. 75: 5264-5271 [Abstract] [Full Text]  
• Raffatellu, M., Santos, R. L., Chessa, D., Wilson, R. P., Winter, S. E., Rossetti, C. A., Lawhon, S. D., Chu, H., Lau, T., Bevins, C. L., Adams, L. G., Baumler, A. J. (2007). The Capsule Encoding the viaB Locus Reduces Interleukin-17 Expression and Mucosal Innate Responses in the Bovine Intestinal Mucosa during Infection with Salmonella enterica Serotype Typhi. Infect. Immun. 75: 4342-4350 [Abstract] [Full Text]  
• Graveline, R., Segura, M., Radzioch, D., Gottschalk, M. (2007). TLR2-dependent recognition of Streptococcus suis is modulated by the presence of capsular polysaccharide which modifies macrophage responsiveness. Int Immunol 19: 375-389 [Abstract] [Full Text]  
• Santander, J., Wanda, S.-Y., Nickerson, C. A., Curtiss, R. III (2007). Role of RpoS in Fine-Tuning the Synthesis of Vi Capsular Polysaccharide in Salmonella enterica Serotype Typhi. Infect. Immun. 75: 1382-1392 [Abstract] [Full Text]  
• Chiu, T. T., Leung, W. Y., Moyer, M. P., Strieter, R. M., Rozengurt, E. (2007). Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-{kappa}B. Am. J. Physiol. Cell Physiol. 292: C767-C777 [Abstract] [Full Text]  
• Kreisman, L. S.C., Friedman, J. H., Neaga, A., Cobb, B. A. (2007). Structure and function relations with a T-cell-activating polysaccharide antigen using circular dichroism. Glycobiology 17: 46-55 [Abstract] [Full Text]  
• Alaniz, R. C., Cummings, L. A., Bergman, M. A., Rassoulian-Barrett, S. L., Cookson, B. T. (2006). Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells. J. Immunol. 177: 3983-3993 [Abstract] [Full Text]  
• Raffatellu, M., Chessa, D., Wilson, R. P., Tukel, C., Akcelik, M., Baumler, A. J. (2006). Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis. Infect. Immun. 74: 19-27 [Full Text]  
• Raffatellu, M., Sun, Y.-H., Wilson, R. P., Tran, Q. T., Chessa, D., Andrews-Polymenis, H. L., Lawhon, S. D., Figueiredo, J. F., Tsolis, R. M., Adams, L. G., Baumler, A. J. (2005). Host Restriction of Salmonella enterica Serotype Typhi Is Not Caused by Functional Alteration of SipA, SopB, or SopD. Infect. Immun. 73: 7817-7826 [Abstract] [Full Text]