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.

DC-SIGN, Dendritic cells, Helicobacter pylori, Phase variation, Th1/Th2 cell response,
The Journal of Experimental Medicine
Department of Medical Microbiology and Infectious Diseases

Bergman, M.P, Appelmelk, B.J, Engering, A, Smits, H.H, van Vliet, S.J, van Bodegraven, A.A, … van Kooyk, Y. (2004). Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. The Journal of Experimental Medicine, 200(8), 979–990. doi:10.1084/jem.20041061