fig1: Clinically isolated H. pylori and purified LPS bind to DC-SIGN. H. pylori strains (•) isolated from patients from different continents (reference 5) and purified LPS (○) were coated on ELISA plates, and binding of recombinant DC-SIGN-Fc was assessed with peroxidase-labeled goat anti–human Fc.

Mentions: DC-SIGN binds Lex and Ley (28), so we investigated whether DC-SIGN functions as a receptor for H. pylori. Several clinical isolates of H. pylori from different continents (5) did bind to DC-SIGN fusion protein, which suggests that the H. pylori cell wall contains a common and universal ligand for DC-SIGN (Fig. 1). H. pylori binds DC-SIGN through its LPS, as was indicated by the binding of several batches of purified H. pylori LPS to DC-SIGN (Fig. 1). For 11 H. pylori strains, both whole bacterial cells and purified LPS were available, and the binding to DC-SIGN of whole cells and purified LPS correlates well (r = 0.8045; P < 0.0028; 95% confidence interval of 0.39–0.95; not depicted). The binding of H. pylori whole cells or purified LPS to DC-SIGN-Fc could be blocked by anti–DC-SIGN antibodies with mannan, or by chelating free Ca2+ ions with EGTA (not depicted), indicating that binding was specific.

Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y, Appelmelk BJ - J. Exp. Med. (2004)

Bottom Line: Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development.In contrast, Le- variants escape binding to DCs and induce a strong Th1 cell response.Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.

Affiliation: Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, The Netherlands.

Abstract: The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le- variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.