The Vi Capsular Polysaccharide of Salmonella Typhi Promotes Macrophage Phagocytosis by Binding the Human C-Type Lectin DC-SIGN
Lillian F. Zhang, Bernd Lepenies, Sayuri Nakamae, Briana M. Young, Renato L. Santos, Manuela Raffatellu, Brian A. Cobb, Hirotaka Hiyoshi, Andreas J. Bäumler
Abstract
serovar Typhi is the causative agent of typhoid fever. The recent emergence of S. Typhi strains which are resistant to antibiotic therapy highlights the importance of vaccination in managing typhoid fever. The virulence-associated (Vi) capsular polysaccharide is an effective vaccine against typhoid fever, but the role the capsule plays during pathogenesis remains incompletely understood. Here, we identify the human C-type lectin receptor DC-SIGN as the receptor for the Vi capsular polysaccharide. Binding of capsulated S. Typhi to DC-SIGN resulted in phagocytosis of the pathogen by macrophages and induction of an anti-inflammatory cytokine response. Thus, the interaction of the Vi capsular polysaccharide with human DC-SIGN contributes to the pathogenesis of typhoid fever and should be further investigated in the context of vaccine development.