Roles of cholesteryl α-glucosides produced by Helicobacter pylori in the interactions with the host immune system.

Helicobacter pylori extracts cholesterol from the host epithelial cells during infection for nutrition and lipid raft formation. However, the presence of cholesterol in invading bacteria facilitates phagocytosis and subsequent immune responses by the host. To evade immune surveillance, H. pylori immediately converts cholesterol to cholesteryl 6'-O-acyl α-glucosides (αCAGs) to prevent phagocytosis by the host. In addition, a part of αCAGs translocate to phagosome membranes where they retard the phagosome maturation and the fusion with lysosomes, thereby prolonging survival in phagocytes. On the other hand, H. pylori αCAGs are possible targets of the host immune system because they are recognized by both invariant Vα14 TCR-bearing NKT (iNKT) cells and the C-type lectin receptor Mincle or Clec4e. iNKT cells produce proinflammatory cytokines when activated by the cytokines secreted by antigen-presenting cells (APCs) recognizing αCAGs via Mincle, while iNKT cells directly recognizing αCAGs with CD1d using invariant Vα14 TCR in a Mincle-independent manner produce both pro- and anti-inflammatory cytokines, suggesting their involvement in the regulation of the immune responses against H. pylori infection. This review classifies and discusses the interactions of H. pylori and the host mediated by cholesterol and its glycoside, αCAG, during infection, focusing on the possible ambivalent roles of iNKT cells in the control of the immune responses to the pathogen producing αCAG.