TY - JOUR
T1 - Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN
AU - Bergman, Mathijs P
AU - Engering, Anneke
AU - Smits, Hermelijn H
AU - van Vliet, Sandra J
AU - van Bodegraven, Ad A
AU - Wirth, Hans-Peter
AU - Kapsenberg, Martien L
AU - Vandenbroucke-Grauls, Christina M J E
AU - van Kooyk, Yvette
AU - Appelmelk, Ben J
PY - 2004/10/18
Y1 - 2004/10/18
N2 - 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.
AB - 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.
KW - Cell Adhesion Molecules/physiology
KW - Fucosyltransferases/physiology
KW - Helicobacter pylori/physiology
KW - Humans
KW - Interleukin-10/biosynthesis
KW - Interleukin-6/biosynthesis
KW - Lectins, C-Type/physiology
KW - Lewis Blood-Group System/physiology
KW - Lewis X Antigen/physiology
KW - Lipopolysaccharides/pharmacology
KW - Membrane Glycoproteins/physiology
KW - Receptors, Cell Surface/physiology
KW - Th1 Cells/immunology
KW - Th2 Cells/immunology
KW - Toll-Like Receptors
U2 - 10.1084/jem.20041061
DO - 10.1084/jem.20041061
M3 - Article
C2 - 15492123
VL - 200
SP - 979
EP - 990
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 8
ER -