Vi polysaccharide ofSalmonella typhitargets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses

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Abstract
Vi capsular polysaccharide (Vi) was first identified as a virulence antigen ofSalmonella typhi, the causative agent of typhoid fever in humans; it rendersS. typhiresistant to phagocytosis and the action of serum complement. However, the role of Vi during the infection of intestinal epithelium withS. typhiis not completely understood. We show here that Vi can interact with a model human intestinal epithelial cell line, Caco-2, through a cell-surface-associated molecular complex containing two major proteins of 30 and 35 kDa and a minor protein of ≈68 kDa. The two major proteins were identified as the putative tumor suppressor molecule, prohibitin, and its closely related homolog, B cell receptor-associated protein 37. These two proteins were enriched in lipid rafts, and Vi readily associated with these membrane microdomains. Engagement of Caco-2 cells with Vi inhibited their ability to produce an inflammatory response upon infection with Vi–S. typhi. Consistent with this effect, infection of Caco-2 cells with Vi+S. typhiproduced less IL-8 compared with Vi–S. typhi. Cells treated with Vi showed reduced extracellular signal-regulated kinase phosphorylation in response to infection with Vi–S. typhior stimulation with phorbol 12-myristate 13-acetate, suggesting that the mitogen-activated protein kinase pathway might be a target for Vi-mediated inhibition of inflammatory responses. These findings reveal a crucial role for Vi in the modulation of early inflammatory responses during infection withS. typhi. This kind of a modulation could play a significant role in the establishment of infection byS. typhi.