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MICROBIOLOGY
Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses
Hybridoma Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India
Communicated by G. Balakrish Nair, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh, October 12, 2004 (received for review August 18, 2004)
Vi capsular polysaccharide (Vi) was first identified as a virulence antigen of Salmonella typhi, the causative agent of typhoid fever in humans; it renders S. typhi resistant to phagocytosis and the action of serum complement. However, the role of Vi during the infection of intestinal epithelium with S. typhi is 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. typhi produced 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. typhi or 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 with S. typhi. This kind of a modulation could play a significant role in the establishment of infection by S. typhi.
Vi capsular polysaccharide | putative tumor suppressor molecule | IL-8
Abbreviations: Vi, Vi capsular polysaccharide; ERK, extracellular signal-regulated kinase; HRP, horseradish peroxidase; NC, nitrocellulose; ECL, enhanced chemiluminescence reagent; PAG, polyacrylamide gel; PMA, phorbol 12-myristate 13-acetate; moi, multiplicity of infection; BAP-37, B cell receptor-associated protein 37; MAP, mitogen-activated protein.
* To whom correspondence should be addressed. E-mail: ayub{at}nii.res.in.
© 2004 by The National Academy of Sciences of the USA
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