The Journal of Experimental Medicine
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Published 18 October 2004. doi:10.1084/jem.20041061
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 8, 979-990
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Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN

Mathijs P. Bergman1,4, Anneke Engering2, Hermelijn H. Smits5, Sandra J. van Vliet2, Ad A. van Bodegraven3, Hans-Peter Wirth6, Martien L. Kapsenberg5, Christina M.J.E. Vandenbroucke-Grauls1, Yvette van Kooyk2, and Ben J. Appelmelk1

1 Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
2 Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
3 Department of Gastroenterology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
4 Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, 3015 GD Rotterdam, Netherlands
5 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
6 Division of Gastroenterology, GastroZentrum Kreuzlingen, 8280 Kreuzlingen, Switzerland

Address correspondence to Ben J. Appelmelk, Dept. of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands. Phone: 31-20-444-8297; Fax: 31-20-444-8318; email: bj.appelmelk{at}vumc.nl

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.

Key Words: Helicobacter pylori • phase variation • DC-SIGN • dendritic cells • Th1/Th2 cell response


M.P. Bergman and A. Engering contributed equally to this work.

Abbreviations used in this paper: AFLP, amplified fragment length polymorphism; Le, Lewis; MOI, multiplicity of infection; MR, mannose receptor; TLR, Toll-like receptor; T reg cell, regulatory T cell.


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