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Infection and Immunity, June 2005, p. 3367-3374, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3367-3374.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Manuela Raffatellu,1 Daniela Chessa,1,2 R. Paul Wilson,1 Richard Dusold,3 Salvatore Rubino,2 and Andreas J. Bäumler1*

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.

* Corresponding author. Present address: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645. Phone: (530) 754-7225. Fax: (530) 754-7240. E-mail: abaumler{at}ucdavis.edu.

Editor: J. T. Barbieri

Infection and Immunity, June 2005, p. 3367-3374, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3367-3374.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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