Published 18 October 2004. doi:10.1084/jem.20041061
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 8, 979-990
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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Pang, P.-C., Tissot, B., Drobnis, E. Z., Sutovsky, P., Morris, H. R., Clark, G. F., Dell, A.
(2007). Expression of Bisecting Type and Lewisx/Lewisy Terminated N-Glycans on Human Sperm. J. Biol. Chem.
282: 36593-36602
[Abstract]
[Full Text]
-
Sterzenbach, T., Lee, S. K., Brenneke, B., von Goetz, F., Schauer, D. B., Fox, J. G., Suerbaum, S., Josenhans, C.
(2007). Inhibitory Effect of Enterohepatic Helicobacter hepaticus on Innate Immune Responses of Mouse Intestinal Epithelial Cells. Infect. Immun.
75: 2717-2728
[Abstract]
[Full Text]
-
Nagai, S., Mimuro, H., Yamada, T., Baba, Y., Moro, K., Nochi, T., Kiyono, H., Suzuki, T., Sasakawa, C., Koyasu, S.
(2007). Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis. Proc. Natl. Acad. Sci. USA
104: 8971-8976
[Abstract]
[Full Text]
-
Ma, B., Simala-Grant, J. L., Taylor, D. E.
(2006). Fucosylation in prokaryotes and eukaryotes. Glycobiology
16: 158R-184R
[Abstract]
[Full Text]
-
Algood, H. M. S., Cover, T. L.
(2006). Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses. Clin. Microbiol. Rev.
19: 597-613
[Abstract]
[Full Text]
-
Naarding, M. A., Dirac, A. M., Ludwig, I. S., Speijer, D., Lindquist, S., Vestman, E.-L., Stax, M. J., Geijtenbeek, T. B. H., Pollakis, G., Hernell, O., Paxton, W. A.
(2006). Bile Salt-Stimulated Lipase from Human Milk Binds DC-SIGN and Inhibits Human Immunodeficiency Virus Type 1 Transfer to CD4+ T Cells.. Antimicrob. Agents Chemother.
50: 3367-3374
[Abstract]
[Full Text]
-
Falkowska, E., Durso, R. J., Gardner, J. P., Cormier, E. G., Arrigale, R. A., Ogawa, R. N., Donovan, G. P., Maddon, P. J., Olson, W. C., Dragic, T.
(2006). L-SIGN (CD209L) isoforms differently mediate trans-infection of hepatoma cells by hepatitis C virus pseudoparticles. J. Gen. Virol.
87: 2571-2576
[Abstract]
[Full Text]
-
Drakes, M. L., Czinn, S. J., Blanchard, T. G.
(2006). Regulation of Murine Dendritic Cell Immune Responses by Helicobacter felis Antigen.. Infect. Immun.
74: 4624-4633
[Abstract]
[Full Text]
-
Kusters, J. G., van Vliet, A. H. M., Kuipers, E. J.
(2006). Pathogenesis of Helicobacter pylori Infection. Clin. Microbiol. Rev.
19: 449-490
[Abstract]
[Full Text]
-
Kao, J. Y., Rathinavelu, S., Eaton, K. A., Bai, L., Zavros, Y., Takami, M., Pierzchala, A., Merchant, J. L.
(2006). Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am. J. Physiol. Gastrointest. Liver Physiol.
291: G73-G81
[Abstract]
[Full Text]
-
He, B., Qiao, X., Klasse, P. J., Chiu, A., Chadburn, A., Knowles, D. M., Moore, J. P., Cerutti, A.
(2006). HIV-1 Envelope Triggers Polyclonal Ig Class Switch Recombination through a CD40-Independent Mechanism Involving BAFF and C-Type Lectin Receptors. J. Immunol.
176: 3931-3941
[Abstract]
[Full Text]
-
Ma, B., Audette, G. F., Lin, S., Palcic, M. M., Hazes, B., Taylor, D. E.
(2006). Purification, Kinetic Characterization, and Mapping of the Minimal Catalytic Domain and the Key Polar Groups of Helicobacter pylori {alpha}-(1,3/1,4)-Fucosyltransferases. J. Biol. Chem.
281: 6385-6394
[Abstract]
[Full Text]
-
Nilsson, C., Skoglund, A., Moran, A. P., Annuk, H., Engstrand, L., Normark, S.
(2006). An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection. Proc. Natl. Acad. Sci. USA
103: 2863-2868
[Abstract]
[Full Text]
-
Davis, C. W., Nguyen, H.-Y., Hanna, S. L., Sanchez, M. D., Doms, R. W., Pierson, T. C.
(2006). West Nile Virus Discriminates between DC-SIGN and DC-SIGNR for Cellular Attachment and Infection. J. Virol.
80: 1290-1301
[Abstract]
[Full Text]
-
Murch, S H
(2005). Probiotics as mainstream allergy therapy?. Arch. Dis. Child.
90: 881-882
[Full Text]
-
Thomas, P. G., Carter, M. R., Da'dara, A. A., DeSimone, T. M., Harn, D. A.
(2005). A Helminth Glycan Induces APC Maturation via Alternative NF-{kappa}B Activation Independent of I{kappa}B{alpha} Degradation. J. Immunol.
175: 2082-2090
[Abstract]
[Full Text]
-
Gagliardi, M. C., Teloni, R., Giannoni, F., Pardini, M., Sargentini, V., Brunori, L., Fattorini, L., Nisini, R.
(2005). Mycobacterium bovis Bacillus Calmette-Guerin infects DC-SIGN- dendritic cell and causes the inhibition of IL-12 and the enhancement of IL-10 production. J. Leukoc. Biol.
78: 106-113
[Abstract]
[Full Text]
-
Pulendran, B.
(2005). Variegation of the Immune Response with Dendritic Cells and Pathogen Recognition Receptors. J. Immunol.
174: 2457-2465
[Abstract]
[Full Text]