The virulence polysaccharide Vi released by Salmonella Typhi targets membrane prohibitin to inhibit T-cell activation.
T cells are critical to immunity against pathogenic Salmonella including Salmonella Typhi which causes systemic infection, typhoid, in humans. The strategies that this pathogen employs to keep T-cell mediated immune responses in check during establishment of systemic infection are not completely understood. Here, we show that the virulence polysaccharide Vi, which distinguishes S. Typhi from localized gastroenteritis-producing nontyphoidal Salmonella serovars, is a potent inhibitor of T-cell activation. Vi released by S. Typhi interacts with the membrane prohibitin complex and inhibits IL-2 secretion from T cells stimulated through the T-cell receptor (TCR) but does not affect PMA-activated interleukin 2 (IL-2) secretion. Treatment with Vi suppresses early activation events including TCR down-regulation, actin polymerization, and phosphorylation of ERK. Coadministration of Vi with anti-CD3 Ab reduces secretion of IL-2 and interferon γ in mice. Our findings reveal a mechanism by which S. Typhi may target T-cell immunity during establishment of typhoid.
Srikanth K
SK
Santhanam
Debjani
D
Dutta
Farhat
F
Parween
Ayub
A
Qadri
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D012485:Salmonella typhi / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D011135:Polysaccharides, Bacterial; D000091402:Prohibitins; D012097:Repressor Proteins; C054154:capsular polysaccharide, Salmonella