Hemoglobin Transforms Anti-Inflammatory Salmonella typhi Virulence Polysaccharide into a TLR-2 Agonist

被引:16
作者
Garg, Rohini [1 ]
Qadri, Ayub [1 ]
机构
[1] Natl Inst Immunol, Hybridoma Lab, New Delhi 110067, India
关键词
VI-CAPSULAR POLYSACCHARIDE; INTESTINAL EPITHELIAL-CELLS; TOLL-LIKE RECEPTORS; INFLAMMATORY RESPONSES; BACTERIAL-INFECTIONS; PROHIBITIN FAMILY; LIPOTEICHOIC ACID; HOST-DEFENSE; INNATE; ACTIVATION;
D O I
10.4049/jimmunol.0903512
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vi capsular polysaccharide is a major virulence determinant of the human typhoid-causing pathogen Salmonella typhi; it is absent in nontyphoidal Salmonella serovars. We show in this study that through its specific interaction with the membrane recognition complex containing the prohibitin family of molecules, Vi can inhibit the production of inflammatory cytokines from mononuclear phagocytes stimulated with Salmonella flagellin. Remarkably, Vi lost this anti-inflammatory capability and switched to a proinflammatory state when cell stimulations were performed in the presence of serum. The serum-transformed proinflammatory form of Vi induced secretion of cytokines from monocytes by specifically engaging TLR-2/TLR-1. The molecule responsible for bringing about this conversion of Vi from an anti-inflammatory to a proinflammatory form was serum-derived hemoglobin. Derivatives of Vi incapable of interacting with hemoglobin did not switch to a proinflammatory state in vitro or in vivo. These findings provide compelling evidence for a role of hemoglobin in transforming the anti-inflammatory S. typhi virulence polysaccharide into an immune activator. The Journal of Immunology, 2010, 184: 5980-5987.
引用
收藏
页码:5980 / 5987
页数:8
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