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.
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18 October 2004
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October 18 2004
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,
Mathijs P. Bergman
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
4Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, 3015 GD Rotterdam, Netherlands
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Anneke Engering,
Anneke Engering
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Hermelijn H. Smits,
Hermelijn H. Smits
5Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Sandra J. van Vliet,
Sandra J. van Vliet
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Ad A. van Bodegraven,
Ad A. van Bodegraven
3Department of Gastroenterology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Hans-Peter Wirth,
Hans-Peter Wirth
6Division of Gastroenterology, GastroZentrum Kreuzlingen, 8280 Kreuzlingen, Switzerland
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Martien L. Kapsenberg,
Martien L. Kapsenberg
5Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Christina M.J.E. Vandenbroucke-Grauls,
Christina M.J.E. Vandenbroucke-Grauls
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Yvette van Kooyk,
Yvette van Kooyk
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Ben J. Appelmelk
Ben J. Appelmelk
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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Mathijs P. Bergman
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
4Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, 3015 GD Rotterdam, Netherlands
Anneke Engering
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
Hermelijn H. Smits
5Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Sandra J. van Vliet
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
Ad A. van Bodegraven
3Department of Gastroenterology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
Hans-Peter Wirth
6Division of Gastroenterology, GastroZentrum Kreuzlingen, 8280 Kreuzlingen, Switzerland
Martien L. Kapsenberg
5Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Christina M.J.E. Vandenbroucke-Grauls
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
Yvette van Kooyk
2Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
Ben J. Appelmelk
1Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands
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: [email protected]
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.
Received:
May 28 2004
Accepted:
August 30 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 200 (8): 979–990.
Article history
Received:
May 28 2004
Accepted:
August 30 2004
Citation
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; Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN . J Exp Med 18 October 2004; 200 (8): 979–990. doi: https://doi.org/10.1084/jem.20041061
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