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, M.P.
AU - Engering, A.J.
AU - Smits, HH
AU - van Vliet, SJ
AU - van Bodegraven, A.A.
AU - Wirth, HP
AU - Kapsenberg, ML
AU - Vandenbroucke-Grauls, C.M.J.E.
AU - van Kooijk, Y.
AU - Appelmelk, B.J.
PY - 2004
Y1 - 2004
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.
UR - https://www.scopus.com/pages/publications/7244246930
UR - https://www.scopus.com/inward/citedby.url?scp=7244246930&partnerID=8YFLogxK
U2 - 10.1084/jem.20041061
DO - 10.1084/jem.20041061
M3 - Article
SN - 0022-1007
VL - 200
SP - 979
EP - 990
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -