THE VI-CAPSULAR ANTIGEN OF SALMONELLA ENTERICA SEROTYPE TYPHI REDUCES TOLL-LIKE RECEPTOR-DEPENDENT IL-8 IN THE INTESTINAL MUCOSA

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.