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

M.P. Bergman, A.J. Engering, HH Smits, SJ van Vliet, A.A. van Bodegraven, HP Wirth, ML Kapsenberg, C.M.J.E. Vandenbroucke-Grauls, Y. van Kooijk, B.J. Appelmelk, Sandra J van Vliet, Hans-Peter Wirth, Martien L Kapsenberg, Yvette van Kooyk

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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.
Original languageEnglish
Pages (from-to)979-90
Number of pages12
JournalJournal of Experimental Medicine
Volume200
Issue number8
DOIs
Publication statusPublished - 18 Oct 2004

Keywords

  • AMC wi-buiten
  • Cell Adhesion Molecules/physiology
  • Fucosyltransferases/physiology
  • Helicobacter pylori/physiology
  • Humans
  • Interleukin-10/biosynthesis
  • Interleukin-6/biosynthesis
  • Lectins, C-Type/physiology
  • Lewis Blood-Group System/physiology
  • Lewis X Antigen/physiology
  • Lipopolysaccharides/pharmacology
  • Membrane Glycoproteins/physiology
  • Receptors, Cell Surface/physiology
  • Th1 Cells/immunology
  • Th2 Cells/immunology
  • Toll-Like Receptors

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