The Vi Capsular Polysaccharide of Salmonella Typhi Promotes Macrophage Phagocytosis by Binding the Human C-Type Lectin DC-SIGN

Capsular polysaccharides are common virulence factors of extracellular, but not intracellular bacterial pathogens, due to the antiphagocytic properties of these surface structures. It is therefore paradoxical that Salmonella enterica subspecies enterica serovar Typhi, an intracellular pathogen, synthesizes a virulence-associated (Vi) capsule, which exhibits antiphagocytic properties. Here, we show that the Vi capsular polysaccharide has different functions when S. Typhi interacts with distinct subsets of host phagocytes. The Vi capsular polysaccharide allowed S. Typhi to selectively evade phagocytosis by human neutrophils while promoting human macrophage phagocytosis. A screen of C-type lectin receptors identified human DC-SIGN as the receptor involved in macrophage binding and phagocytosis of capsulated S. Typhi. Consistent with the anti-inflammatory activity of DC-SIGN, purified Vi capsular polysaccharide reduced inflammatory responses in macrophages. These data suggest that binding of the human C-type lectin receptor DC-SIGN by the Vi capsular polysaccharide contributes to the pathogenesis of typhoid fever.