Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN.
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.
Bergman
Mathijs P
MP
Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Center, 1081 BT Amsterdam, The Netherlands.
Engering
Anneke
A
Smits
Hermelijn H
HH
van Vliet
Sandra J
SJ
van Bodegraven
Ad A
AA
Wirth
Hans-Peter
HP
Kapsenberg
Martien L
ML
Vandenbroucke-Grauls
Christina M J E
CM
van Kooyk
Yvette
Y
Appelmelk
Ben J
BJ
D015815:Cell Adhesion Molecules / Q000502:physiology*; D005647:Fucosyltransferases / Q000502:physiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000502:physiology*; D007983:Lewis Blood Group Antigens / Q000502:physiology; D016256:Lewis X Antigen / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D051193:Toll-Like Receptors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D005647:Fucosyltransferases; D016753:Interleukin-10; D015850:Interleukin-6; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C094162:Lewis Y antigen; C031692:galactoside 3-fucosyltransferase