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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.

Helicobacter pylori, cytokine, Immunotherapy, allergy, immunomodulation, steryl glycoside, invariant NKT cell, IgE

NCBI PubMed ID: 22934809
Publication DOI: 10.2174/092986712803341502
Journal NLM ID: 9440157
Publisher: Saif Zone, Sharjah, U.A.E.: Bentham Science Publishers
Correspondence: Shimamura M
Institutions: Tsukuba Research Center for Interdisciplinary Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan, Foundation for Advancement of International Science, Tsukuba, Japan, Mitsubishi Kagaku Institute of Life Sciences, Mashida, Japan

A chloroform-methanol-extracted lipid of Helicobacter pylori was studied. Three kinds of glycolipids, accounting for about 25% (wt/wt) of the total lipid, were detected and identified to be cholesteryl glucosides. The structures of two of them were determined to be cholesteryl-α-D-glucopyranoside and cholesteryl-6-O-tetrade-canoyl-α-D-glucopyranoside, and the plausible structure of the third one was identified as cholesteryl-6-O-phosphatidyl-α-D-glucopyranoside. Cholesteryl glucosides are very rare in animals and bacteria. Furthermore, those in H. pylori had an α-glycosidic linkage, which is rather unusual for natural glycosides, and a phosphate-linked cholesteryl glycoside like the cholesteryl-6-O-phosphatidyl-α-D-glucopyranoside has not been reported previously. As the cholesterol glucosides were detected in strains obtained from diverse geographical locations, the presence of cholesteryl glucosides in H. pylori is a very unique and a characteristic feature of the species. These findings add a new facet to the physiology and biochemistry, especially the cholesterol and glucose metabolism, of H. pylori. Furthermore, the cholesteryl glucosides of H. pylori showed hemolytic activities.

Helicobacter pylori, cholesteryl glycosides

NCBI PubMed ID: 7665522
Publication DOI: 10.1128/jb.177.18.5327-5333.1995
Journal NLM ID: 2985120R
Publisher: American Society for Microbiology
Institutions: Department of Bacteriology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama, Japan, Department of Cell Chemistry, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama, Japan, Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan
Methods: 1H NMR, NMR-2D, FAB-MS, TLC, acid hydrolysis, GLC, biological assays, methanolysis, alkaline hydrolysis, enzymatic digestion, extraction, optical rotation measurement, column chromatography, cell growth, derivatization, orcinol-sulfuric acid assay

Helicobacter pylori infection causes gastric pathology such as ulcer and carcinoma. Because H. pylori is auxotrophic for cholesterol, we have explored the assimilation of cholesterol by H. pylori in infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glucosylation. Excessive cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells, such as macrophages and dendritic cells, and enhances antigen-specific T cell responses. A cholesterol-rich diet during bacterial challenge leads to T cell-dependent reduction of the H. pylori burden in the stomach. Intrinsic alpha-glucosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. We identify the gene hp0421 as encoding the enzyme cholesterol-alpha-glucosyltransferase responsible for cholesterol glucosylation. Generation of knockout mutants lacking hp0421 corroborates the importance of cholesteryl glucosides for escaping phagocytosis, T cell activation and bacterial clearance in vivo. Thus, we propose a mechanism regulating the host-pathogen interaction whereby glucosylation of a lipid tips the scales towards immune evasion or response.

Helicobacter pylori, cholesterol glycoside

NCBI PubMed ID: 16951684
Publication DOI: 10.1038/nm1480
Journal NLM ID: 9502015
Publisher: New York, NY: Nature Publishing Company
Correspondence: Wunder C ; Meyer TF
Institutions: Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany, Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany, Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz, Berlin, Germany, Biozentrum Klein Flottbek, University of Hamburg, Hamburg, Germany, Institute of Pathology, Otto von Guericke University, Magdeburg, Germany, Core Facility Microarray, Max Planck Institute for Infection Biology, Berlin, Germany, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA, Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
Methods: DNA techniques, TLC, biological assays, extraction, cell growth, centrifugation

Natural killer T-cells, with an invariant T-cell antigen receptor α-chain (iNKT cells), are unique and conserved subset of lymphocytes capable of altering the immune system through their rapid and potent cytokine responses. They are reactive to lipid antigens presented by the CD1d molecule, an antigen-presenting molecule that is not highly polymorphic. iNKT cell responses frequently involve mixtures of cytokines that work against each other, and therefore attempts are underway to develop synthetic antigens that elicit only strong interferon-gamma (IFNγ) or only strong interleukin-4 responses but not both. Strong IFNγ responses may correlate with tighter binding to CD1d and prolonged stimulation of iNKT cells, and this may be useful for vaccine adjuvants and for stimulating anti-tumor responses. iNKT cells are self-reactive although the structure of the endogenous antigen is controversial. By contrast, bacterial and fungal lipids that engage the T-cell receptor and activate IFNγ from iNKT cells have been identified from both pathogenic and commensal organisms and the responses are in some cases highly protective from pathogens in mice. It is possible that the expanding knowledge of iNKT cell antigens and iNKT cell activation will provide the basis for therapies for patients suffering from infectious and immune diseases and cancer.

glycolipid, immune system, natural killer T-cells

NCBI PubMed ID: 27013447
Publication DOI: 10.1016/j.bj.2016.01.003
Journal NLM ID: 101599820
Publisher: New York, NY: Elsevier
Correspondence: Kronenberg M
Institutions: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, USA, Division of Biological Sciences, University of California, San Diego, USA

The structure, properties, distribution in nature, and biological activity of sterol glycosides and acylgylcosides are reviewed.

biological activity, sterol glycoside, acylgylcoside

Publication DOI: 10.1007/BF02323277
Journal NLM ID: 0151571
Publisher: Tashkent: Izdatelstvo Fan
Institutions: Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141, Belarus, Minsk, Ul. Akad. Kuprevicha, 5/2, Belarus