Therapeutic Potential of Cholesteryl O-acyl α-glucoside Found in Helicobacter pylori

M.      Shimamura; H.      Hidaka

Abstract

Steryl glycosides are derivatives of sterols where the 3β-hydroxy group is glycosylated. Some of them are further converted to steryl O-acyl glycosides. Steryl glycosides and their derivatives are widely distributed in plants, algae, and fungi, but are relatively rarely distributed in bacteria and animals. Accumulating evidence suggests that glycosylation of sterols not only modifies physicochemical properties of cell membranes but also alters immunogenicity of the cells. Helicobacter pylori, that colonizes the stomach and causes gastric diseases, is auxotrophic for cholesterol, so that it extracts this lipid from plasma membranes of epithelial cells of the host stomach. Since incorporation of cholesterol promotes immune responses of the host, Helicobacter pylori converts cholesterol to cholesteryl glucoside (ChG) and then to cholesteryl 6'-O-acyl glucoside (ChAcG) to evade the immune surveillance. We have found that ChAcG thus produced is specifically recognized by invariant Vα14-Jα18 TCR+ (Vα14) NKT cells in a CD1-dependent manner. We have also found that activation of Vα14 NKT cells by administration of ChAcG retains homeostasis of immunity upon exposure to allergens and reduces the incidence of allergy. In this article, overview of immunological functions of steryl glycosides with an emphasis on the immunoregulatory functions of ChAcG, is demonstrated.

Keywords: Steryl glycoside, invariant NKT cell, Helicobacter pylori, immunomodulation, cytokine, allergy, IgE, immunotherapy