Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN

Mathijs P Bergman, Anneke Engering, Hermelijn H Smits, Sandra J van Vliet, Ad A van Bodegraven, Hans-Peter Wirth, Martien L Kapsenberg, Christina M J E Vandenbroucke-Grauls, Yvette van Kooyk, Ben J Appelmelk

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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.

Original languageEnglish
Pages (from-to)979-90
Number of pages12
JournalJournal of Experimental Medicine
Issue number8
Publication statusPublished - 18 Oct 2004

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