The Vi Capsular Antigen ofSalmonella entericaSerotype Typhi Reduces Toll-Like Receptor-Dependent Interleukin-8 Expression in the Intestinal Mucosa

Abstract

Human infections with nontyphoidal

The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion

“…S. Typhi is the causative agent of typhoid fever, a severe systemic infection in which neutrophils are scarce in intestinal infiltrates (Sprinz et al, 1966;Mukawi, 1978;Kraus et al, 1999;Nguyen et al, 2004) and fecal leucocyte populations (Harris et al, 1972;Alvarado, 1983;Guyot et al, 1984). Infection of human colonic tissue explants with a nontyphoidal Salmonella serotype, S. Typhimurium, results in expression of the neutrophil chemoattractant interleukin (IL)-8, but this response is not observed during infection with S. Typhi (Raffatellu et al, 2005). These data illustrate that S. Typhi possesses virulence mechanisms that prevent the induction of host responses leading to neutrophil recruitment in the intestinal mucosa (Raffatellu et al, 2006).…”

“…S. Typhi isolates that spontaneously lost the ability to produce the Vi antigen elicit significantly more IL-8 secretion in Caco-2 cells than Vi-producing clinical isolates (Sharma and Qadri, 2004). A precise deletion of the viaB locus significantly increases IL-8 expression elicited by S. Typhi in polarized T84 monolayers and in human colonic biopsy samples (Raffatellu et al, 2005). These data identify the viaB locus as a S. Typhi-specific DNA region involved in reducing expression of neutrophil chemoattractants in human colonic tissue explants and in colonic epithelial cancer cells (Raffatellu et al, 2006).…”

Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium

“…To detect this translocation event occurring during infection, we employed a ␤-lactamase reporter system utilized previously by our group to visualize translocation of the Salmonella Typhi Type III secretion effector SipA (26). For this purpose, we expressed S. Typhimurium FliC from a derivative of the broad host range plasmid pBBR1MCS, pFlagTEM-1, in which fliC is expressed from the Trc promoter.…”

“…A flgB mutant was obtained by transduction of flgB6148::MudJ into IR715 from TH8460 (obtained from K. Hughes) using the bacteriophage P22HTint. A fliC::Tn10 fljB::MudJ mutant (EHW26) was obtained from the Bäumler laboratory (26). For macrophage infection, S. Typhimurium was grown in Luria-Bertani (LB) broth to late logarithmic phase to maximize expression of the Salmonella pathogenicity island 1-encoded Type III secretion system (T3SS-1), as described previously (21).…”

Host Specificity of Bacterial Pathogens

“…However, S. Typhi does not elicit overt host responses during the initial invasion of the intestinal mucosa, as indicated by a 2-wk incubation period of typhoid fever . S. Typhi avoids the generation of responses during the initial phase of infection because it evades innate immunity by expressing a capsular polysaccharide (Raffatellu et al 2005;Wilson et al 2008;Haneda et al 2009) and by rapidly repressing expression of flagella and T3SS-1 during the transition through the epithelial lining (Winter et al 2010b). These mechanisms enable S. Typhi to slip past the host's defenses to cause an invasive bloodstream infection.…”