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Gangliosides in the Immune System: Role of Glycosphingolipids and Glycosphingolipid-Enriched Lipid Rafts in Immunological Functions

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1804))

Abstract

Although individuals are constantly exposed to infectious agents, these agents are generally resisted by the innate and acquired immune systems. Both the innate and acquired immune systems protect against invading organisms, but they differ functionally in several ways. The innate immune system is the body’s inborn defense mechanism and the first line of defense against invading organisms, such as bacteria, fungi, and viruses. Glycosphingolipids (GSLs), which are expressed on the outer leaflet of plasma membranes (Murate et al., J Cell Sci 128(8):1627–1638, 2015), are involved in both innate and acquired immunity (Inokuchi et al., Biochim Biophys Acta 1851(1):98–106, 2015; Nakayama et al., Arch Immunol Ther Exp (Warsz) 61(3):217–228, 2013; Rueda, Br J Nutr 98(Suppl 1):S68–73, 2007; Popa and Portoukalian, Pathol Biol (Paris) 51(5):253–255, 2003).

Recent studies have indicated that innate immunity is not a “nonspecific” immune system. Large numbers of viruses, bacteria, and bacterial toxins have been reported to bind to host surface carbohydrates, a number of which are components of GSLs (Schengrund, Biochem Pharmacol 65(5):699–707, 2003). Binding studies have also demonstrated that some glycolipids function as receptors for microorganisms and bacterial toxins (Yates and Rampersaud, Ann N Y Acad Sci 845:57–71, 1998). These findings clearly indicate that GSLs are involved in host–pathogen interactions.

GSLs are composed of hydrophobic ceramide and hydrophilic sugar moieties (Hakomori, Annu Rev Biochem 50:733–764, 1980). The ceramide moiety of sphingolipids and the cholesterol sterol-ring system are thought to interact via hydrogen bonds and hydrophobic van der Waal’s forces (Mukherjee and Maxfield, Annu Rev Cell Dev Biol 20:839–866, 2004). Additional hydrophilic cis interactions among GSL headgroups have been found to promote their lateral associations with surrounding lipid and protein membrane components. These interactions result in the separation in cell membranes of lipid rafts, which are lipid domains rich in GSLs, cholesterol, glycosylphosphatidylinositol (GPI)-anchored proteins and membrane-anchored signaling molecules (Pike, J Lipid Res 47(7):1597–1598, 2006). These GSL-enriched lipid rafts play important roles in immunological functions (Inokuchi et al., Biochim Biophys Acta 1851(1):98–106, 2015; Iwabuchi et al., Mediators Inflamm 2015:120748, 2015; Anderson and Roche, Biochim Biophys Acta 1853(4):775–780, 2015; Zuidscherwoude et al., J Leukoc Biol 95(2):251–263, 2014; Dykstra et al., Annu Rev Immunol 21:457–481, 2003). This introductory chapter describes the roles of GSLs and their lipid rafts in the immune system.

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References

  1. Murate M, Abe M, Kasahara K, Iwabuchi K, Umeda M, Kobayashi T (2015) Transbilayer distribution of lipids at nano scale. J Cell Sci 128(8):1627–1638. https://doi.org/10.1242/jcs.163105

    Article  PubMed  CAS  Google Scholar 

  2. Inokuchi J, Nagafuku M, Ohno I, Suzuki A (2015) Distinct selectivity of gangliosides required for CD4(+) T and CD8(+) T cell activation. Biochim Biophys Acta 1851(1):98–106. https://doi.org/10.1016/j.bbalip.2014.07.013

    Article  PubMed  CAS  Google Scholar 

  3. Nakayama H, Ogawa H, Takamori K, Iwabuchi K (2013) GSL-enriched membrane microdomains in innate immune responses. Arch Immunol Ther Exp 61(3):217–228. https://doi.org/10.1007/s00005-013-0221-6

    Article  CAS  Google Scholar 

  4. Rueda R (2007) The role of dietary gangliosides on immunity and the prevention of infection. Br J Nutr 98(Suppl 1):S68–S73. https://doi.org/10.1017/s0007114507832946

    Article  PubMed  CAS  Google Scholar 

  5. Popa I, Portoukalian J (2003) Relationship between lipids and cutaneous immunity: example of the gangliosides. Pathol Biol (Paris) 51(5):253–255

    Article  CAS  Google Scholar 

  6. Schengrund CL (2003) “Multivalent” saccharides: development of new approaches for inhibiting the effects of glycosphingolipid-binding pathogens. Biochem Pharmacol 65(5):699–707

    Article  PubMed  CAS  Google Scholar 

  7. Yates AJ, Rampersaud A (1998) Sphingolipids as receptor modulators. An overview. Ann N Y Acad Sci 845:57–71

    Article  PubMed  CAS  Google Scholar 

  8. Hakomori S (1981) Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu Rev Biochem 50:733–764. https://doi.org/10.1146/annurev.bi.50.070181.003505

    Article  PubMed  CAS  Google Scholar 

  9. Mukherjee S, Maxfield FR (2004) Membrane domains. Annu Rev Cell Dev Biol 20:839–866. https://doi.org/10.1146/annurev.cellbio.20.010403.095451

    Article  PubMed  CAS  Google Scholar 

  10. Pike LJ (2006) Rafts defined: a report on the keystone symposium on lipid rafts and cell function. J Lipid Res 47(7):1597–1598. https://doi.org/10.1194/jlr.E600002-JLR200

    Article  PubMed  CAS  Google Scholar 

  11. Iwabuchi K, Nakayama H, Oizumi A, Suga Y, Ogawa H, Takamori K (2015) Role of ceramide from glycosphingolipids and its metabolites in immunological and inflammatory responses in humans. Mediat Inflamm 2015:120748. https://doi.org/10.1155/2015/120748

    Article  CAS  Google Scholar 

  12. Anderson HA, Roche PA (2015) MHC class II association with lipid rafts on the antigen presenting cell surface. Biochim Biophys Acta 1853(4):775–780. https://doi.org/10.1016/j.bbamcr.2014.09.019

    Article  PubMed  CAS  Google Scholar 

  13. Zuidscherwoude M, de Winde CM, Cambi A, van Spriel AB (2014) Microdomains in the membrane landscape shape antigen-presenting cell function. J Leukoc Biol 95(2):251–263. https://doi.org/10.1189/jlb.0813440

    Article  PubMed  CAS  Google Scholar 

  14. Dykstra M, Cherukuri A, Sohn HW, Tzeng SJ, Pierce SK (2003) Location is everything: lipid rafts and immune cell signaling. Annu Rev Immunol 21:457–481. https://doi.org/10.1146/annurev.immunol.21.120601.141021

    Article  PubMed  CAS  Google Scholar 

  15. Tsai B, Gilbert JM, Stehle T, Lencer W, Benjamin TL, Rapoport TA (2003) Gangliosides are receptors for murine polyoma virus and SV40. EMBO J 22(17):4346–4355

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Naroeni A, Porte F (2002) Role of cholesterol and the ganglioside GM(1) in entry and short-term survival of Brucella suis in murine macrophages. Infect Immun 70(3):1640–1644

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Cuatrecasas P (1973) Vibrio cholerae choleragenoid. Mechanism of inhibition of cholera toxin action. Biochemistry 12(18):3577–3581

    Article  PubMed  CAS  Google Scholar 

  18. Cuatrecasas P (1973) Gangliosides and membrane receptors for cholera toxin. Biochemistry 12(18):3558–3566

    Article  PubMed  CAS  Google Scholar 

  19. Hyun CS, Kimmich GA (1984) Interaction of cholera toxin and Escherichia coli enterotoxin with isolated intestinal epithelial cells. Am J Phys 247(6 Pt 1):G623–G631

    CAS  Google Scholar 

  20. Otnaess AB, Laegreid A, Ertresvag K (1983) Inhibition of enterotoxin from Escherichia coli and vibrio cholerae by gangliosides from human milk. Infect Immun 40(2):563–569

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Bronnum H, Seested T, Hellgren LI, Brix S, Frokiaer H (2005) Milk-derived GM(3) and GD(3) differentially inhibit dendritic cell maturation and effector functionalities. Scand J Immunol 61(6):551–557. https://doi.org/10.1111/j.1365-3083.2005.01566.x

    Article  PubMed  CAS  Google Scholar 

  22. Takenouchi H, Kiyokawa N, Taguchi T, Matsui J, Katagiri YU, Okita H, Okuda K, Fujimoto J (2004) Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells. J Cell Sci 117(Pt 17):3911–3922

    Article  PubMed  CAS  Google Scholar 

  23. Lingwood CA (1996) Role of verotoxin receptors in pathogenesis. Trends Microbiol 4(4):147–153

    Article  PubMed  CAS  Google Scholar 

  24. Louise CB, Kaye SA, Boyd B, Lingwood CA, Obrig TG (1995) Shiga toxin-associated hemolytic uremic syndrome: effect of sodium butyrate on sensitivity of human umbilical vein endothelial cells to Shiga toxin. Infect Immun 63(7):2766–2769

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Tyrrell GJ, Ramotar K, Toye B, Boyd B, Lingwood CA, Brunton JL (1992) Alteration of the carbohydrate binding specificity of verotoxins from gal alpha 1-4Gal to GalNAc beta 1-3Gal alpha 1-4Gal and vice versa by site-directed mutagenesis of the binding subunit. Proc Natl Acad Sci U S A 89(2):524–528

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Mukai T, Kaneko S, Matsumoto M, Ohori H (2004) Binding of Bifidobacterium bifidum and lactobacillus reuteri to the carbohydrate moieties of intestinal glycolipids recognized by peanut agglutinin. Int J Food Microbiol 90(3):357–362

    Article  PubMed  CAS  Google Scholar 

  27. de Bentzmann S, Roger P, Dupuit F, Bajolet-Laudinat O, Fuchey C, Plotkowski MC, Puchelle E (1996) Asialo GM1 is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells. Infect Immun 64(5):1582–1588

    PubMed  PubMed Central  Google Scholar 

  28. Sato T, Iwabuchi K, Nagaoka I, Adachi Y, Ohno N, Tamura H, Seyama K, Fukuchi Y, Nakayama H, Yoshizaki F, Takamori K, Ogawa H (2006) Induction of human neutrophil chemotaxis by Candida albicans-derived beta-1,6-long glycoside side-chain-branched beta-glucan. J Leukoc Biol 80(1):204–211. https://doi.org/10.1189/jlb.0106069

    Article  PubMed  CAS  Google Scholar 

  29. Angstrom J, Teneberg S, Milh MA, Larsson T, Leonardsson I, Olsson BM, Halvarsson MO, Danielsson D, Naslund I, Ljungh A, Wadstrom T, Karlsson KA (1998) The lactosylceramide binding specificity of helicobacter pylori. Glycobiology 8(4):297–309

    Article  PubMed  CAS  Google Scholar 

  30. Hahn PY, Evans SE, Kottom TJ, Standing JE, Pagano RE, Limper AH (2003) Pneumocystis carinii cell wall beta-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. J Biol Chem 278(3):2043–2050

    Article  PubMed  CAS  Google Scholar 

  31. Karlsson KA (1986) Animal glycolipids as attachment sites for microbes. Chem Phys Lipids 42(1–3):153–172

    Article  PubMed  CAS  Google Scholar 

  32. Saukkonen K, Burnette WN, Mar VL, Masure HR, Tuomanen EI (1992) Pertussis toxin has eukaryotic-like carbohydrate recognition domains. Proc Natl Acad Sci U S A 89(1):118–122

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Zimmerman JW, Lindermuth J, Fish PA, Palace GP, Stevenson TT, DeMong DE (1998) A novel carbohydrate-glycosphingolipid interaction between a beta-(1-3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes. J Biol Chem 273(34):22014–22020

    Article  PubMed  CAS  Google Scholar 

  34. Fukuda MN, Dell A, Oates JE, Wu P, Klock JC, Fukuda M (1985) Structures of glycosphingolipids isolated from human granulocytes. The presence of a series of linear poly-N-acetyllactosaminylceramide and its significance in glycolipids of whole blood cells. J Biol Chem 260(2):1067–1082

    PubMed  CAS  Google Scholar 

  35. Teneberg S, Angstrom J, Ljungh A (2004) Carbohydrate recognition by enterohemorrhagic Escherichia coli: characterization of a novel glycosphingolipid from cat small intestine. Glycobiology 14(2):187–196

    Article  PubMed  CAS  Google Scholar 

  36. Stromberg N, Karlsson KA (1990) Characterization of the binding of propionibacterium granulosum to glycosphingolipids adsorbed on surfaces. An apparent recognition of lactose which is dependent on the ceramide structure. J Biol Chem 265(19):11244–11250

    PubMed  CAS  Google Scholar 

  37. Stromberg N, Ryd M, Lindberg AA, Karlsson KA (1988) Studies on the binding of bacteria to glycolipids. Two species of Propionibacterium apparently recognize separate epitopes on lactose of lactosylceramide. FEBS Lett 232(1):193–198

    Article  PubMed  CAS  Google Scholar 

  38. Payne D, Tatham D, Williamson ED, Titball RW (1998) The pH 6 antigen of Yersinia pestis binds to beta1-linked galactosyl residues in glycosphingolipids. Infect Immun 66(9):4545–4548

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Jansson L, Tobias J, Lebens M, Svennerholm AM, Teneberg S (2006) The major subunit, CfaB, of colonization factor antigen i from enterotoxigenic Escherichia coli is a glycosphingolipid binding protein. Infect Immun 74(6):3488–3497

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Stromberg N, Deal C, Nyberg G, Normark S, So M, Karlsson KA (1988) Identification of carbohydrate structures that are possible receptors for Neisseria gonorrhoeae. Proc Natl Acad Sci U S A 85(13):4902–4906

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Backenson PB, Coleman JL, Benach JL (1995) Borrelia burgdorferi shows specificity of binding to glycosphingolipids. Infect Immun 63(8):2811–2817

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Nakayama H, Kurihara H, Morita YS, Kinoshita T, Mauri L, Prinetti A, Sonnino S, Yokoyama N, Ogawa H, Takamori K, Iwabuchi K (2016) Lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils. Sci Signal 9(449):ra101. https://doi.org/10.1126/scisignal.aaf1585

    Article  CAS  PubMed  Google Scholar 

  43. Newburg DS, Chaturvedi P (1992) Neutral glycolipids of human and bovine milk. Lipids 27(11):923–927

    Article  CAS  PubMed  Google Scholar 

  44. Iwabuchi K, Nagaoka I (2002) Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils. Blood 100(4):1454–1464

    PubMed  CAS  Google Scholar 

  45. Minguet S, Klasener K, Schaffer AM, Fiala GJ, Osteso-Ibanez T, Raute K, Navarro-Lerida I, Hartl FA, Seidl M, Reth M, Del Pozo MA (2017) Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance. Nat Immunol 18:1150. https://doi.org/10.1038/ni.3813

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Shrestha D, Exley MA, Vereb G, Szollosi J, Jenei A (2014) CD1d favors MHC neighborhood, GM1 ganglioside proximity and low detergent sensitive membrane regions on the surface of B lymphocytes. Biochim Biophys Acta 1840(1):667–680

    Article  PubMed  CAS  Google Scholar 

  47. Kimata H (1994) GM1, a ganglioside that specifically enhances immunoglobulin production and proliferation in human plasma cells. Eur J Immunol 24(11):2910–2913. https://doi.org/10.1002/eji.1830241149

    Article  PubMed  CAS  Google Scholar 

  48. Gupta N, DeFranco AL (2007) Lipid rafts and B cell signaling. Semin Cell Dev Biol 18(5):616–626. https://doi.org/10.1016/j.semcdb.2007.07.009

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Maity PC, Blount A, Jumaa H, Ronneberger O, Lillemeier BF, Reth M (2015) B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation. Sci Signal 8(394):ra93. https://doi.org/10.1126/scisignal.2005887

    Article  PubMed  CAS  Google Scholar 

  50. Harder T, Rentero C, Zech T, Gaus K (2007) Plasma membrane segregation during T cell activation: probing the order of domains. Curr Opin Immunol 19(4):470–475. https://doi.org/10.1016/j.coi.2007.05.002

    Article  PubMed  CAS  Google Scholar 

  51. Popik W, Alce TM (2004) CD4 receptor localized to non-raft membrane microdomains supports HIV-1 entry. Identification of a novel raft localization marker in CD4. J Biol Chem 279(1):704–712. https://doi.org/10.1074/jbc.M306380200

    Article  PubMed  CAS  Google Scholar 

  52. Nagafuku M, Okuyama K, Onimaru Y, Suzuki A, Odagiri Y, Yamashita T, Iwasaki K, Fujiwara M, Takayanagi M, Ohno I, Inokuchi JI (2012) CD4 and CD8 T cells require different membrane gangliosides for activation. Proc Natl Acad Sci U S A 109(6):E336–E342. https://doi.org/10.1073/pnas.1114965109

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kuziemko GM, Stroh M, Stevens RC (1996) Cholera toxin binding affinity and specificity for gangliosides determined by surface plasmon resonance. Biochemistry 35(20):6375–6384. https://doi.org/10.1021/bi952314i

    Article  PubMed  CAS  Google Scholar 

  54. Masserini M, Freire E, Palestini P, Calappi E, Tettamanti G (1992) Fuc-GM1 ganglioside mimics the receptor function of GM1 for cholera toxin. Biochemistry 31(8):2422–2426

    Article  PubMed  CAS  Google Scholar 

  55. Yanagisawa M, Ariga T, Yu RK (2006) Cholera toxin B subunit binding does not correlate with GM1 expression: a study using mouse embryonic neural precursor cells. Glycobiology 16(9):19G–22G

    Article  PubMed  CAS  Google Scholar 

  56. Kanda N, Tamaki K (1998) Ganglioside GQ1b enhances Ig production by human PBMCs. J Allergy Clin Immunol 102(5):813–820

    Article  PubMed  CAS  Google Scholar 

  57. Medzhitov R, Janeway C Jr (2000) Innate immune recognition: mechanisms and pathways. Immunol Rev 173:89–97

    Article  PubMed  CAS  Google Scholar 

  58. Liang S, Wang M, Tapping RI, Stepensky V, Nawar HF, Triantafilou M, Triantafilou K, Connell TD, Hajishengallis G (2007) Ganglioside GD1a is an essential coreceptor for toll-like receptor 2 signaling in response to the B subunit of type IIb enterotoxin. J Biol Chem 282(10):7532–7542. https://doi.org/10.1074/jbc.M611722200

    Article  PubMed  CAS  Google Scholar 

  59. McNamara N, Gallup M, Sucher A, Maltseva I, McKemy D, Basbaum C (2006) AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2. Am J Respir Cell Mol Biol 34(6):653–660. https://doi.org/10.1165/rcmb.2005-0441OC

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Blander JM, Medzhitov R (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304(5673):1014–1018

    Article  PubMed  CAS  Google Scholar 

  61. Doyle SE, O'Connell RM, Miranda GA, Vaidya SA, Chow EK, Liu PT, Suzuki S, Suzuki N, Modlin RL, Yeh WC, Lane TF, Cheng G (2004) Toll-like receptors induce a phagocytic gene program through p38. J Exp Med 199(1):81–90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Ezekowitz RA, Sastry K, Bailly P, Warner A (1990) Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells. J Exp Med 172(6):1785–1794

    Article  PubMed  CAS  Google Scholar 

  63. Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, Huber M, Kalis C, Keck S, Galanos C, Freudenberg M, Beutler B (2005) CD14 is required for MyD88-independent LPS signaling. Nat Immunol 6(6):565–570

    Article  PubMed  CAS  Google Scholar 

  64. Elomaa O, Kangas M, Sahlberg C, Tuukkanen J, Sormunen R, Liakka A, Thesleff I, Kraal G, Tryggvason K (1995) Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell 80(4):603–609

    Article  PubMed  CAS  Google Scholar 

  65. Peiser L, Gough PJ, Kodama T, Gordon S (2000) Macrophage class a scavenger receptor-mediated phagocytosis of Escherichia coli: role of cell heterogeneity, microbial strain, and culture conditions in vitro. Infect Immun 68(4):1953–1963

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Herre J, Marshall AS, Caron E, Edwards AD, Williams DL, Schweighoffer E, Tybulewicz V, Reis e Sousa C, Gordon S, Brown GD (2004) Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 104(13):4038–4045

    Article  PubMed  CAS  Google Scholar 

  67. Brown EJ (1991) Complement receptors and phagocytosis. Curr Opin Immunol 3(1):76–82

    Article  PubMed  CAS  Google Scholar 

  68. Iwabuchi K, Prinetti A, Sonnino S, Mauri L, Kobayashi T, Ishii K, Kaga N, Murayama K, Kurihara H, Nakayama H, Yoshizaki F, Takamori K, Ogawa H, Nagaoka I (2008) Involvement of very long fatty acid-containing lactosylceramide in lactosylceramide-mediated superoxide generation and migration in neutrophils. Glycoconj J 25(4):357–374. https://doi.org/10.1007/s10719-007-9084-6

    Article  PubMed  CAS  Google Scholar 

  69. Nakayama H, Yoshizaki F, Prinetti A, Sonnino S, Mauri L, Takamori K, Ogawa H, Iwabuchi K (2008) Lyn-coupled LacCer-enriched lipid rafts are required for CD11b/CD18-mediated neutrophil phagocytosis of nonopsonized microorganisms. J Leukoc Biol 83(3):728–741. https://doi.org/10.1189/jlb.0707478

    Article  PubMed  CAS  Google Scholar 

  70. Arnaout MA (1990) Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 75(5):1037–1050

    PubMed  CAS  Google Scholar 

  71. Evangelista V, Pamuklar Z, Piccoli A, Manarini S, Dell'elba G, Pecce R, Martelli N, Federico L, Rojas M, Berton G, Lowell CA, Totani L, Smyth SS (2007) Src family kinases mediate neutrophil adhesion to adherent platelets. Blood 109(6):2461–2469

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Piccardoni P, Manarini S, Federico L, Bagoly Z, Pecce R, Martelli N, Piccoli A, Totani L, Cerletti C, Evangelista V (2004) SRC-dependent outside-in signalling is a key step in the process of autoregulation of beta2 integrins in polymorphonuclear cells. Biochem J 380(Pt 1):57–65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Rabb H, Michishita M, Sharma CP, Brown D, Arnaout MA (1993) Cytoplasmic tails of human complement receptor type 3 (CR3, CD11b/CD18) regulate ligand avidity and the internalization of occupied receptors. J Immunol 151(2):990–1002

    PubMed  CAS  Google Scholar 

  74. Dedhar S, Hannigan GE (1996) Integrin cytoplasmic interactions and bidirectional transmembrane signalling. Curr Opin Cell Biol 8(5):657–669

    Article  PubMed  CAS  Google Scholar 

  75. Vetvicka V, Thornton BP, Ross GD (1996) Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest 98(1):50–61. https://doi.org/10.1172/JCI118777

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Wright SD, Levin SM, Jong MT, Chad Z, Kabbash LG (1989) CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-asp-containing peptides and a second site for bacterial lipopolysaccharide. J Exp Med 169(1):175–183

    Article  PubMed  CAS  Google Scholar 

  77. Chiricozzi E, Ciampa MG, Brasile G, Compostella F, Prinetti A, Nakayama H, Ekyalongo RC, Iwabuchi K, Sonnino S, Mauri L (2015) Direct interaction, instrumental for signaling processes, between LacCer and Lyn in the lipid rafts of neutrophil-like cells. J Lipid Res 56(1):129–141. https://doi.org/10.1194/jlr.M055319

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Manes S, del Real G, Martinez AC (2003) Pathogens: raft hijackers. Nat Rev Immunol 3(7):557–568

    Article  PubMed  CAS  Google Scholar 

  79. Peyron P, Bordier C, N'Diaye EN, Maridonneau-Parini I (2000) Nonopsonic phagocytosis of mycobacterium kansasii by human neutrophils depends on cholesterol and is mediated by CR3 associated with glycosylphosphatidylinositol-anchored proteins. J Immunol 165(9):5186–5191

    Article  PubMed  CAS  Google Scholar 

  80. Gatfield J, Pieters J (2000) Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288(5471):1647–1650

    Article  PubMed  CAS  Google Scholar 

  81. Vieira OV, Botelho RJ, Grinstein S (2002) Phagosome maturation: aging gracefully. Biochem J 366(Pt 3):689–704. https://doi.org/10.1042/BJ20020691

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Armstrong JA, Hart PD (1975) Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival. J Exp Med 142(1):1–16

    Article  PubMed  CAS  Google Scholar 

  83. Stuart ES, Webley WC, Norkin LC (2003) Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells. Exp Cell Res 287(1):67–78

    Article  PubMed  CAS  Google Scholar 

  84. Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN (1997) Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389(6651):636–639

    Article  PubMed  CAS  Google Scholar 

  85. Watarai M, Makino S, Fujii Y, Okamoto K, Shirahata T (2002) Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication. Cell Microbiol 4(6):341–355

    Article  PubMed  CAS  Google Scholar 

  86. Tamilselvam B, Daefler S (2008) Francisella targets cholesterol-rich host cell membrane domains for entry into macrophages. J Immunol 180(12):8262–8271

    Article  PubMed  CAS  Google Scholar 

  87. Harrison RE, Brumell JH, Khandani A, Bucci C, Scott CC, Jiang X, Finlay BB, Grinstein S (2004) Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles. Mol Biol Cell 15(7):3146–3154. https://doi.org/10.1091/mbc.E04-02-0092

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Gekara NO, Weiss S (2004) Lipid rafts clustering and signalling by listeriolysin O. Biochem Soc Trans 32(Pt 5):712–714

    Article  PubMed  CAS  Google Scholar 

  89. Knodler LA, Vallance BA, Hensel M, Jackel D, Finlay BB, Steele-Mortimer O (2003) Salmonella type III effectors PipB and PipB2 are targeted to detergent-resistant microdomains on internal host cell membranes. Mol Microbiol 49(3):685–704

    Article  PubMed  CAS  Google Scholar 

  90. Brumell JH, Kujat-Choy S, Brown NF, Vallance BA, Knodler LA, Finlay BB (2003) SopD2 is a novel type III secreted effector of salmonella typhimurium that targets late endocytic compartments upon delivery into host cells. Traffic 4(1):36–48

    Article  PubMed  CAS  Google Scholar 

  91. Kaur D, Obregon-Henao A, Pham H, Chatterjee D, Brennan PJ, Jackson M (2008) Lipoarabinomannan of mycobacterium: mannose capping by a multifunctional terminal mannosyltransferase. Proc Natl Acad Sci U S A 105(46):17973–17977. https://doi.org/10.1073/pnas.0807761105

    Article  PubMed  PubMed Central  Google Scholar 

  92. Fratti RA, Chua J, Vergne I, Deretic V (2003) Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci U S A 100(9):5437–5442. https://doi.org/10.1073/pnas.0737613100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Briken V, Porcelli SA, Besra GS, Kremer L (2004) Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol 53(2):391–403. https://doi.org/10.1111/j.1365-2958.2004.04183.x

    Article  PubMed  CAS  Google Scholar 

  94. Schlesinger LS (1993) Macrophage phagocytosis of virulent but not attenuated strains of mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol 150(7):2920–2930

    PubMed  CAS  Google Scholar 

  95. Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B, Van Kooyk Y (2003) Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med 197(1):7–17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Kang PB, Azad AK, Torrelles JB, Kaufman TM, Beharka A, Tibesar E, DesJardin LE, Schlesinger LS (2005) The human macrophage mannose receptor directs mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med 202(7):987–999. https://doi.org/10.1084/jem.20051239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Shukla S, Richardson ET, Athman JJ, Shi L, Wearsch PA, McDonald D, Banaei N, Boom WH, Jackson M, Harding CV (2014) Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its cell envelope localization to control phagolysosomal fusion. PLoS Pathog 10(10):e1004471. https://doi.org/10.1371/journal.ppat.1004471

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Gaur RL, Ren K, Blumenthal A, Bhamidi S, Gonzalez-Nilo FD, Jackson M, Zare RN, Ehrt S, Ernst JD, Banaei N (2014) LprG-mediated surface expression of lipoarabinomannan is essential for virulence of mycobacterium tuberculosis. PLoS Pathog 10(9):e1004376. https://doi.org/10.1371/journal.ppat.1004376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Diacovich L, Gorvel JP (2010) Bacterial manipulation of innate immunity to promote infection. Nat Rev Microbiol 8(2):117–128. https://doi.org/10.1038/nrmicro2295

    Article  PubMed  CAS  Google Scholar 

  100. Mishra AK, Driessen NN, Appelmelk BJ, Besra GS (2011) Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev 35(6):1126–1157. https://doi.org/10.1111/j.1574-6976.2011.00276.x

    Article  PubMed  CAS  Google Scholar 

  101. Dell’Angelica EC, Mullins C, Caplan S, Bonifacino JS (2000) Lysosome-related organelles. FASEB J 14(10):1265–1278

    Article  PubMed  Google Scholar 

  102. Kniep B, Skubitz KM (1998) Subcellular localization of glycosphingolipids in human neutrophils. J Leukoc Biol 63(1):83–88

    Article  PubMed  CAS  Google Scholar 

  103. Mohn H, Le Cabec V, Fischer S, Maridonneau-Parini I (1995) The src-family protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation. Biochem J 309(Pt 2):657–665

    Article  PubMed  PubMed Central  Google Scholar 

  104. Peyron P, Maridonneau-Parini I, Stegmann T (2001) Fusion of human neutrophil phagosomes with lysosomes in vitro: involvement of tyrosine kinases of the Src family and inhibition by mycobacteria. J Biol Chem 276(38):35512–35517. https://doi.org/10.1074/jbc.M104399200

    Article  PubMed  CAS  Google Scholar 

  105. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Sato H, Kondo E, Harada M, Koseki H, Nakayama T, Tanaka Y, Taniguchi M (1998) Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells. Proc Natl Acad Sci U S A 95(10):5690–5693

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M (1997) CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278(5343):1626–1629

    Article  PubMed  CAS  Google Scholar 

  107. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI (2012) Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol 12(12):845–857

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Kain L, Webb B, Anderson BL, Deng S, Holt M, Costanzo A, Zhao M, Self K, Teyton A, Everett C, Kronenberg M, Zajonc DM, Bendelac A, Savage PB, Teyton L (2014) The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian alpha-linked glycosylceramides. Immunity 41(4):543–554

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Nagata M, Izumi Y, Ishikawa E, Kiyotake R, Doi R, Iwai S, Omahdi Z, Yamaji T, Miyamoto T, Bamba T, Yamasaki S (2017) Intracellular metabolite beta-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proc Natl Acad Sci U S A 114(16):E3285–E3294

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Iwabuchi, K. (2018). Gangliosides in the Immune System: Role of Glycosphingolipids and Glycosphingolipid-Enriched Lipid Rafts in Immunological Functions. In: Sonnino, S., Prinetti, A. (eds) Gangliosides. Methods in Molecular Biology, vol 1804. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8552-4_4

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