Skip to main content
SpringerLink
Log in

Immunological Functions of Steryl Glycosides

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Steryl glycosides, sterols glycosylated at the 3β-hydroxy group, have been widely found in plants, algae, and fungi, but are rare in bacteria and animals. Glycosylation of sterols is known to modify properties of the cell membrane and confer resistance against stresses by freezing or heat-shock on cells. Furthermore, accumulating evidence obtained from recent research suggests important biological functions of steryl glycosides, including regulation of host defenses against pathogens, lipid metabolism, and developmental events. This review is focused on the immunological functions of steryl glycosides, such as modulation of host immune functions upon exposure to cholesteryl glycosides produced by pathogenic bacteria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ChG:

Cholesteryl glucoside

ChAcG:

Cholesteryl 6′-O-acyl α-glucopyranoside

ChPG:

Cholesteryl 6′-O-phosphatidyl α-glucopyranoside

SG:

Steryl glycoside

iNKT:

Cell invariant Vα14-Jα18 TCR α-bearing NKT cell

References

  • Abraham W, Wertz PW, Burken RR, Downing DT (1987) Glucosylsterol and acylglucosylsterol of snake epidermis: structure determination. J Lipid Res 28:446–449

    PubMed  CAS  Google Scholar 

  • Akiyama H, Sasaki N, Hanazawa S, Gotoh M, Kobayashi S, Hirabayashi Y, Murakami-Murofushi K (2011) Novel sterol glucosyltransferase in the animal tissue and cultured cells: evidence that glucosylceramide as glucose donor. Biochim Biophys Acta 1811:314–322

    Article  PubMed  CAS  Google Scholar 

  • Bendelac A, Rivera MN, Park SH, Roark JH (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15:535–562

    Article  PubMed  CAS  Google Scholar 

  • Ben-Menachem G, Kubler-Kielb J, Coxon B, Yergey A, Schneerson R (2003) A newly discovered cholesteryl galactoside from Borrelia burgdorferi. Proc Natl Acad Sci USA 100:7913–7918

    Article  PubMed  CAS  Google Scholar 

  • Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K, Van Jaarsveld PP (1996) Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination. Int J Immunopharmacol 18:693–700

    Article  PubMed  CAS  Google Scholar 

  • Bouic PJ (2001) The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr Metab Care 4:471–475

    Article  PubMed  CAS  Google Scholar 

  • Brennan PJ, Tatituri RVV, Brigl M, Kim EY, Tuli A, Sanderson JP, Gadola SD, Hsu F-F, Besra GS, Brenner MB (2011) Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat Immunol 12:1202–1212

    Article  PubMed  CAS  Google Scholar 

  • Brigl M, Tatituri RVV, Watts GEM, Bhowruth V, Leadbetter EA, Barton N, Cohen NR, Hsu F-F, Besra GS, Brenner MB (2011) Innate and cytokine-driven signals, rather than microbial antigen, dominate in natural killer T cell activation during microbial infection. J Exp Med 208:1163–1177

    Article  PubMed  CAS  Google Scholar 

  • Bukholm G, Tannaes T, Nedenskov P, Esbensen Y, Grav HJ, Hovig T, Ariansen S, Guldvog I (1997) Colony variation of Helicobacter pylori: pathogenic potential is correlated to cell wall lipid composition. Scand J Gastroenterol 2:445–454

    Article  Google Scholar 

  • Chang Y-J, Kim HY, Albacker LA, Lee HH, Baumgarth N, Akira S, Savage PB, Endo S, Yamamura T, Maaskant J, Kitano N, Singh A, Bhatt A, Besra GS, van den Elzen P, Appelmelk B, Franck RW, Chen G, DeKruyff RH, Shimamura M, Illarionov P, Umetsu DT (2011) Influenza a infection in suckling mice expands a population of NKT cells that protects mice as adults from airway hyperreactivity. J Clin Invest 121: 57–69

    Article  PubMed  CAS  Google Scholar 

  • Donald PR, Lamprecht JH, Freestone M, Albrecht CF, Bouic PJ, Kotze D, van Jaarsveld PP (1997) A randomised placebo-controlled trial of the efficacy of beta-sitosterol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis 1:518–522

    PubMed  CAS  Google Scholar 

  • Eaton KA, Ringler SR, Danon SJ (1999) Murine splenocytes induce severe gastritis and delayed-type hypersensitivity and suppress bacterial colonization in Helicobacter pylori-infected SCID mice. Infect Immun 67:4594–4602

    PubMed  CAS  Google Scholar 

  • Ernst PB, Gold BD (2000) The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 54:615–640

    Article  PubMed  CAS  Google Scholar 

  • Elyakov GB, Kalinovskaya N, Stonik VA, Kznetsova TA (1980) Glycosides of marineinvertebrates.6.Steroid glycosides from holothurian Stichopus japonicus. Comp Biochem Physiol B: Biochem Mol Bio 33:309–314

    Google Scholar 

  • Grill S, Zaslawski A, Thiele S, Plat J, Warnecke D (2010) The functions of steryl glycosides come to those who wait: recent advances in plants, fungi, bacteria and animals. Prog Lipid Res 49:262–288

    Article  Google Scholar 

  • Gerhard M, Lehn N, Neumeyer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for bloodgroup antigen-binding adhesin. Proc Natl Acad Sci USA 96:12778–12783

    Google Scholar 

  • Hara A, Taketomi T (1982) Isolation and determination of cholesterol glucuronide in human liver. Lipids 17:515–518

    Article  PubMed  CAS  Google Scholar 

  • Hirai Y, Haque M, Yoshida T, Yokota K, Yasuda T, Oguma K (1995) Unique cholesteryl glucosides in Helicobacter pylori: composition and structural analysis. J Bacteriol 177:5327–5333

    PubMed  CAS  Google Scholar 

  • Hoshina H, Tsuchida A, Kametani K, Mori M, Nishizawa T, Suzuki T, Nakamura H, Lee H, Ito Y, Kobayashi M, Masumoto J, Fujita M, Fukada M, Nakayama J (2011) Membrane-associated activation of cholesterol α-glucosyltransferase, an enzyme responsible for biosynthesis of cholesterol-α-d-glucoside in Helicobacter pylori critical for its survival. J Histochem Cytochem 59:98–105

    Article  Google Scholar 

  • Hossain H, Wellensiek HJ, Geyer R, Lochnit G (2001) Structural analysis of glycolipids from Borrelia burgdorferi. Biochimie 83:683–692

    Article  PubMed  CAS  Google Scholar 

  • Jahan N, Almed W, Malik JJ (1995) New steroidal glycosides from Mimusops elengi. Nat Prod 58:1244–1247

    Article  CAS  Google Scholar 

  • Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Borén T (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279:373–377

    Article  PubMed  CAS  Google Scholar 

  • Kawakubo M, Ito Y, Okimura Y, Kobayashi M, Sakura K, Kasama S, Fukuda MN, Fukuda M, Katsuyama T, Nakayama J (2004) Natural antibiotic function of a human gastric mucin against Helicobacter pylori infection. Science 305:1003–1006

    Article  PubMed  CAS  Google Scholar 

  • Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Taniguchi M (1997) CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278:1626–1629

    Article  PubMed  CAS  Google Scholar 

  • Kinjo Y, Wu D, Kim G, Xing G-W, Poles A, Ho DD, Tsuji M, Kawahara K, Wong C-H, Kronenberg M (2005) Recognition of bacterial glycosphingolipids by natural killer T cell. Nature (Lond) 434:520–525

    Article  CAS  Google Scholar 

  • Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M (2006) Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7:978–986

    Article  PubMed  CAS  Google Scholar 

  • Kovganko NV, Kashkan ZN (1999) Sterol glycosides and acylglycosides. Chem Nat Compd 35:479–497

    Article  CAS  Google Scholar 

  • Kunimoto S, Kobayashi T, Kobayashi S, Murakami-Murofushi K (2000) Expression of cholesteryl glucoside by heat shock in human fibroblasts. Cell Stress Chaperon 5:3–7

    Article  CAS  Google Scholar 

  • Kunimoto S, Murofushi W, Kai H, Ishida Y, Uchiyama A, Kobayashi T, Murofushi H, Murakami-Murofushi K (2002) Steryl glucoside is a lipid mediator in stress-responsive signal transduction. Cell Struct Funct 27:157–162

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Lee JY, Park JH, Jung HS, Kim JS, Kang SS, Kim YS, Han Y (2007) Immunoregulatory activity by daucosterol, a beta-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine 25:3834–3840

    Article  PubMed  CAS  Google Scholar 

  • Lepage M (1964) Isolation and characterization of an esterified form of steryl glucoside. J Lipid Res 5:587–592

    PubMed  Google Scholar 

  • Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW, Yamaoka Y, Graham DY, Perez-Trallero E, Wadstrom T, Suerbaum S, Achtman M (2007) An African origin for the intimate association between humans and Helicobacter pylori. Nature 445:915–918

    Article  PubMed  Google Scholar 

  • Lundgren A, Trollmo C, Edebo A, Svennerholm AM, Lundin BS (2005) Helicobacter pylori-specific CD4+ T cells home to and accumulate in the human Helicobacter pylori-infected gastric mucosa. Infect Immun 73:5612–5619

    Article  PubMed  CAS  Google Scholar 

  • Mahdavi J, Sondén B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarström L, Borén T (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297:573–578

    Article  PubMed  CAS  Google Scholar 

  • Marshall BJ, Warren JB (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311–1315

    Article  PubMed  CAS  Google Scholar 

  • Mattner J, DeBord KI, Ismail N, Goff RD, Cantu C III, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutner B, Teyton L, Savage PB, Bendelac A (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature (Lond) 434:525–529

    Article  CAS  Google Scholar 

  • Mayberry WR, Smith PF (1983) Structures and properties of acyl diglucosylcholesterol and galactofuranosyl diacylglycerol from Acholeplasma axanthum. Biochim Biophys Acta 752:434–443

    Article  PubMed  CAS  Google Scholar 

  • Muhiudeen IA, Koerner TA, Samuelsson B, Hirabayashi Y, DeGasperi R, Li SC, Li YT (1984) Characterization of human liver 3-O-beta-d-glucopyranuronosyl-cholesterol by mass spectrometry and nuclear magnetic resonance spectroscopy. J Lipid Res 25:1117–1123

    PubMed  CAS  Google Scholar 

  • Nagai S, Mimuro H, Yamada T, Baba Y, Moro K, Nochi T, Kiyono H, Suzuki T, Sasakawa C, Koyasu S (2007) Role of Peyer’s patches in the induction of Helicobacter pylori-induced gastritis. Proc Natl Acad Sci USA 104:8971–8976

    Article  PubMed  CAS  Google Scholar 

  • Natori T, Koezuka Y, Higa T (1993) Agelasphins, novel α-galactosylceramides from the marine sponge Agelas Mauritianus. Tetrahedron Lett 34:5591–5592

    Article  CAS  Google Scholar 

  • O'Keeffe J, Gately CM, O'Donoghue Y, Zulquernain SA, Stevens FM, Moran AP (2008) Natural killer cell receptor T-lymphocytes in normal and Helicobacter pylori-infected human gastric mucosa. Helicobacter 13:500–505

    Google Scholar 

  • Pappo J, Torrey D, Castriotta L, Savinainen A, Kavok Z, Ibraghimov A (1999) Helicobacter pylori infection in immunized mice lacking major histocompatibility complex class I and class II functions. Infect Immun 67:337–341

    PubMed  CAS  Google Scholar 

  • Peek RM Jr, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2:28–37

    Article  PubMed  CAS  Google Scholar 

  • Power FB, Tutin F (1908) The constituents of olive bark. J Chem Soc Trans 93:904–914

    Article  CAS  Google Scholar 

  • Power FB, Salway AH (1913) The identification of ipuranol and some allied compounds as phytosterol glucosides. J Chem Soc Trans 103:399–406

    Article  CAS  Google Scholar 

  • Salway AH (1913) The synthetical preparation of the d-glucosides of sitosterol, cholesterol, and some fatty alcohols. J Chem Soc Trans 103:1022–1029

    Article  CAS  Google Scholar 

  • Schröder NW, Schombel U, Heine H, Gobel UB, Zähringer U, Schumann RR (2003) Acylated cholesteryl galactoside as a novel immunogenic motif in Borrelia burgdorferi sensu stricto. J Biol Chem 278:33645–33653

    Article  PubMed  Google Scholar 

  • Shimamura M, Ohteki T, Beutner U, MacDonald HR (1997) Lack of directed Vα14-Jα281 rearrangements in NK1+T cells. Eur J Immunol 27:1576–1579

    Article  PubMed  CAS  Google Scholar 

  • Shimamura M, Huang Y-Y (2002) Presence of a novel subset of NKT cells bearing an invariant Vα19.1-Jα26 TCR α chain. FEBS Lett 516:97–100

    Article  PubMed  CAS  Google Scholar 

  • Shimamura M, Huang Y-Y, Okamoto N, Watanabe Y, Murakami R, Kinoshita T, Hirabayashi Y, Murakata C, Ito Y, Ogawa T (2007) Glycolipids with non-reducing end α-mannosyl residues that have potentials to activate invariant Vα19 NKT cells. FEBS J 274:2921–2932

    Article  PubMed  CAS  Google Scholar 

  • Shimomura H, Hosoda K, Hayashi S, Yokota K, Oguma K, Hirai Y (2009) Steroids mediate resistance to the bactericidal effect of phosphatidylcholines against Helicobacter pylori. FEMS Microbiol Lett 301:84–94

    Article  PubMed  CAS  Google Scholar 

  • Simons K, Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 33:269–295

    Article  PubMed  CAS  Google Scholar 

  • Stübs G, Fingerle V, Wilske B, Gobel UB, Zähringer U, Schumann RR, Schröder NW (2009) Acylated cholesteryl galactosides are specific antigens of Borrelia causing Lyme disease and frequently induce antibodies in late stages of disease. J Biol Chem 284:13326–13334

    Article  PubMed  Google Scholar 

  • Stübs G, Fingerle V, Zähringer U, Schumann RR, Rademann J, Schröder NWJ (2011) Acylated cholesteryl galactosides are ubiquitous glycolipid antigens among Borrelia burgdorferi sensu lato. FEMS Immunol Med Microbiol 63:140–143

    Article  PubMed  Google Scholar 

  • Taketomi T, Hara A, Kasama T (1982) Abnormalities in cerebral lipids and hepatic cholesterol glucuronide of a patient with GM1-gangliosidosis type 2. Adv Exp Med Biol 152:291–305

    PubMed  CAS  Google Scholar 

  • Tannaes T, Grav HJ, Bukholm G (2000) Lipid profiles of Helicobacter pylori colony variants. APMIS 108:349–356

    Article  PubMed  CAS  Google Scholar 

  • Tannaes T, Bukholm G (2005) Cholesteryl-6-O-acyl-alpha-d-glucopyranoside of Helicobacter pylori relate to relative lysophospholipid content. FEMS Microbiol Lett 244:117–120

    Article  PubMed  CAS  Google Scholar 

  • Tannaes T, Bukholm IK, Bukholm G (2005) High relative content of lysophospholipids of Helicobacter pylori mediates increased risk for ulcer disease. FEMS Immunol Med Microbiol 44:17–23

    Article  PubMed  CAS  Google Scholar 

  • Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789

    Article  PubMed  CAS  Google Scholar 

  • Wertz PW, Stover PM, Abraham W, Downing DT (1986) Lipids of chicken epidermis. J Lipid Res 27:427–435

    PubMed  CAS  Google Scholar 

  • Wunder C, Churin Y, Winau F, Warnecke D, Vieth M, Lindner B, Zähringer U, Mollenkopf HJ, Heinz E, Meyer TF (2006) Cholesterol glucosylation promotes immune evasion by Helicobacter pylori. Nat Med 12:1030–1038

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Studies on the activation of invariant NKT cells with Helicobacter pylori cholesteryl glycosides were performed by the collaboration with Drs. Petr Illarionov (University of Birmingham) and Dale T. Umetsu (Harvard Medical School). The author thanks them for providing this opportunity of collaboration. This work was supported by a grant from the Ministry of Health, Welfare, and Labor of Japan and a grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 20570146).

Conflict of interest

The author declares that he has no conflict of interest.

Author information

Authors and Affiliations

  1. Tukuba Research Center for Interdisciplinary Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8571, Japan

    Michio Shimamura

  2. Foundation for Advancement of International Science, Tsukuba, Japan

    Michio Shimamura

Authors
  1. Michio Shimamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michio Shimamura.

About this article

Cite this article

Shimamura, M. Immunological Functions of Steryl Glycosides. Arch. Immunol. Ther. Exp. 60, 351–359 (2012). https://doi.org/10.1007/s00005-012-0190-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-012-0190-1

Keywords

Search

Navigation