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Journal of Clinical Immunology

, Volume 31, Issue 1, pp 10–21 | Cite as

Expanding the Universe of Cytokines and Pattern Recognition Receptors: Galectins and Glycans in Innate Immunity

  • Juan P. Cerliani
  • Sean R. Stowell
  • Iván D. Mascanfroni
  • Connie M. Arthur
  • Richard D. Cummings
  • Gabriel A. Rabinovich
Article

Abstract

Effective immunity relies on the recognition of pathogens and tumors by innate immune cells through diverse pattern recognition receptors (PRRs) that lead to initiation of signaling processes and secretion of pro- and anti-inflammatory cytokines. Galectins, a family of endogenous lectins widely expressed in infected and neoplastic tissues have emerged as part of the portfolio of soluble mediators and pattern recognition receptors responsible for eliciting and controlling innate immunity. These highly conserved glycan-binding proteins can control immune cell processes through binding to specific glycan structures on pathogens and tumors or by acting intracellularly via modulation of selective signaling pathways. Recent findings demonstrate that various galectin family members influence the fate and physiology of different innate immune cells including polymorphonuclear neutrophils, mast cells, macrophages, and dendritic cells. Moreover, several pathogens may actually utilize galectins as a mechanism of host invasion. In this review, we aim to highlight and integrate recent discoveries that have led to our current understanding of the role of galectins in host–pathogen interactions and innate immunity. Challenges for the future will embrace the rational manipulation of galectin–glycan interactions to instruct and shape innate immunity during microbial infections, inflammation, and cancer.

Keywords

Microbes innate immunity galectins neutrophils macrophages mast cells dendritic cells glycoimmunology pattern recognition receptors cytokines 

Notes

Acknowledgements

We apologize to the many authors whose papers could not be cited owing to space limitations. Supported by grants from Fundación Sales (Argentina), Agencia Nacional de Promoción Científica y Tecnológica (FONCYT, PICT 2006-603; Argentina), Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET; Argentina) to G.A.R., and by NIH grant HL085607 to R.D.C.

References

  1. 1.
    Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Geijtenbeek TB, Gringhuis SI. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol. 2009;7:465–79.CrossRefGoogle Scholar
  3. 3.
    van Kooyk Y, Rabinovich GA. Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol. 2008;6:593–601.CrossRefGoogle Scholar
  4. 4.
    Marth JD, Grewal PK. Mammalian glycosylation in immunity. Nat Rev Immunol. 2008;11:874–87.CrossRefGoogle Scholar
  5. 5.
    Toscano MA, Ilarregui JM, Bianco GA, Campagna L, Croci DO, Salatino M, et al. Dissecting the pathophysiologic role of endogenous lectins: glycan-binding proteins with cytokine-like activity? Cytokine Growth Factor Rev. 2007;18:57–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Rabinovich GA, Toscano MA. Turning ‘sweet’ on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol. 2009;5:338–52.CrossRefGoogle Scholar
  7. 7.
    Rabinovich GA, Toscano MA, Jackson SS, Vasta GR. Functions of cell surface galectin-glycoprotein lattices. Curr Opin Struct Biol. 2007;5:513–20.CrossRefGoogle Scholar
  8. 8.
    Rabinovich GA, Iglesias MM, Modesti NM, Castagna LF, Wolfenstein-Todel C, Riera CM, et al. Activated rat macrophages produce a galectin-1-like protein that induces apoptosis of T cells: biochemical and functional characterization. J Immunol. 1998;10:4831–40.Google Scholar
  9. 9.
    Ilarregui JM, Croci DO, Bianco GA, Toscano MA, Salatino M, Vermeulen ME, et al. Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol. 2009;9:981–91.CrossRefGoogle Scholar
  10. 10.
    Chen HY, Sharma BB, Yu L, Zuberi R, Weng IC, Kawakami Y, et al. Role of galectin-3 in mast cell functions: galectin-3-deficient mast cells exhibit impaired mediator release and defective JNK expression. J Immunol. 2006;8:4991–7.Google Scholar
  11. 11.
    Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, et al. Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med. 2003;8:1201–12.CrossRefGoogle Scholar
  12. 12.
    Garin MI, Chu CC, Golshayan D, Cernuda-Morollón E, Wait R, Lechler RI. Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood. 2007;5:2058–65.CrossRefGoogle Scholar
  13. 13.
    Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med. 2008;10:e17.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith DF, Song X, Cummings RD. Use of glycan microarrays to explore specificity of glycan-binding proteins. Methods Enzymol. 2010;480:417–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Vasta GR. Roles of galectins in infection. Nat Rev Microbiol. 2009;6:424–38.CrossRefGoogle Scholar
  16. 16.
    Rabinovich GA, Gruppi A. Galectins as immunoregulators during infectious processes: from microbial invasion to the resolution of the disease. Parasite Immunol. 2005;4:103–14.CrossRefGoogle Scholar
  17. 17.
    Laderach DJ, Compagno D, Toscano MA, Croci DO, Dergan-Dylon S, Salatino M, et al. Dissecting the signal transduction pathways triggered by galectin-glycan interactions in physiological and pathological settings. IUBMB Life. 2010;1:1–13.Google Scholar
  18. 18.
    Rabinovich GA, Ilarregui JM. Conveying glycan information into T-cell homeostatic programs: a challenging role for galectin-1 in inflammatory and tumor microenvironments. Immunol Rev. 2009;1:144–59.CrossRefGoogle Scholar
  19. 19.
    Cooper D, Ilarregui JM, Pesoa SA, Croci DO, Perretti M, Rabinovich GA. Multiple functional targets of the immunoregulatory activity of galectin-1 control of immune cell trafficking, dendritic cell physiology, and T-cell fate. Methods Enzymol. 2010;480:199–244.PubMedCrossRefGoogle Scholar
  20. 20.
    Sato S, Nieminen J. Seeing strangers or announcing “danger”: galectin-3 in two models of innate immunity. Glycoconj J. 2004;19:583–91.PubMedCrossRefGoogle Scholar
  21. 21.
    van den Berg TK, Honing H, Franke N, van Remoortere A, Schiphorst WE, Liu FT, et al. LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition. J Immunol. 2004;3:1902–7.Google Scholar
  22. 22.
    John CM, Jarvis GA, Swanson KV, Leffler H, Cooper MD, Huflejt ME, et al. Galectin-3 binds lactosaminylated lipooligosaccharides from Neisseria gonorrhoeae and is selectively expressed by mucosal epithelial cells that are infected. Cell Microbiol. 2002;10:649–62.CrossRefGoogle Scholar
  23. 23.
    Pelletier I, Sato S. Specific recognition and cleavage of galectin-3 by Leishmania major through species-specific polygalactose epitope. J Biol Chem. 2002;20:17663–70.CrossRefGoogle Scholar
  24. 24.
    Silva-Monteiro E, Reis Lorenzato L, Kenji Nihei O, Junqueira M, Rabinovich GA, Hsu DK, et al. Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanosoma cruzi infection. Am J Pathol. 2007;2:546–56.CrossRefGoogle Scholar
  25. 25.
    Dong S, Hughes RC. Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). Glycoconj J. 1997;2:267–74.CrossRefGoogle Scholar
  26. 26.
    Debierre-Grockiego F, Niehus S, Coddeville B, Elass E, Poirier F, Weingart R, et al. Binding of Toxoplasma gondii glycosylphosphatidylinositols to galectin-3 is required for their recognition by macrophages. J Biol Chem. 2010;43:32744–50.CrossRefGoogle Scholar
  27. 27.
    Fradin C, Poulain D, Jouault T. beta-1,2-linked oligomannosides from Candida albicans bind to a 32-kilodalton macrophage membrane protein homologous to the mammalian lectin galectin-3. Infect Immun. 2000;8:4391–8.CrossRefGoogle Scholar
  28. 28.
    Kohatsu L, Hsu DK, Jegalian AG, Liu FT, Baum LG. Galectin-3 induces death of Candida species expressing specific beta-1,2-linked mannans. J Immunol. 2006;7:4718–26.Google Scholar
  29. 29.
    Garner OB, Aguilar HC, Fulcher JA, Levroney EL, Harrison R, Wright L, et al. Endothelial galectin-1 binds to specific glycans on Nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation. PLoS Pathog. 2010;7:e1000993.CrossRefGoogle Scholar
  30. 30.
    Levroney EL, Aguilar HC, Fulcher JA, Kohatsu L, Pace KE, Pang M, et al. Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines. J Immunol. 2005;1:413–20.Google Scholar
  31. 31.
    Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, et al. Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol. 2002;6:2153–67.CrossRefGoogle Scholar
  32. 32.
    Klinman NR. The “clonal selection hypothesis” and current concepts of B cell tolerance. Immunity. 1996;3:189–95.CrossRefGoogle Scholar
  33. 33.
    Stowell SR, Arthur CM, Mehta P, Slanina KA, Blixt O, Leffler H, et al. Galectin-1, -2, and -3 exhibit differential recognition of sialylated glycans and blood group antigens. J Biol Chem. 2008;15:10109–23.CrossRefGoogle Scholar
  34. 34.
    Stowell SR, Arthur CM, Slanina KA, Horton JR, Smith DF, Cummings RD. Dimeric Galectin-8 induces phosphatidylserine exposure in leukocytes through polylactosamine recognition by the C-terminal domain. J Biol Chem. 2008;29:20547–59.CrossRefGoogle Scholar
  35. 35.
    Stowell SR, Arthur CM, Dias-Baruffi M, Rodrigues LC, Gourdine JP, Heimburg-Molinaro J, et al. Innate immune lectins kill bacteria expressing blood group antigen. Nat Med. 2010;3:295–301.CrossRefGoogle Scholar
  36. 36.
    Ouellet M, Mercier S, Pelletier I, Bounou S, Roy J, Hirabayashi J, et al. Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells. J Immunol. 2005;7:4120–6.Google Scholar
  37. 37.
    Mercier S, St-Pierre C, Pelletier I, Ouellet M, Tremblay MJ, Sato S. Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology. 2008;1:121–9.CrossRefGoogle Scholar
  38. 38.
    Gauthier S, Pelletier I, Ouellet M, Vargas A, Tremblay MJ, Sato S, et al. Induction of galectin-1 expression by HTLV-I Tax and its impact on HTLV-I infectivity. Retrovirology. 2008;5:105.PubMedCrossRefGoogle Scholar
  39. 39.
    Okumura CY, Baum LG, Johnson PJ. Galectin-1 on cervical epithelial cells is a receptor for the sexually transmitted human parasite Trichomonas vaginalis. Cell Microbiol. 2008;10:2078–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Fowler M, Thomas RJ, Atherton J, Roberts IS, High NJ. Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion. Cell Microbiol. 2006;1:44–54.CrossRefGoogle Scholar
  41. 41.
    Kamhawi S, Ramalho-Ortigao M, Pham VM, Kumar S, Lawyer PG, Turco SJ, et al. A role for insect galectins in parasite survival. Cell. 2005;3:329–41.CrossRefGoogle Scholar
  42. 42.
    Pelletier I, Hashidate T, Urashima T, Nishi N, Nakamura T, Futai M, et al. Specific recognition of Leishmania major poly-beta-galactosyl epitopes by galectin-9: possible implication of galectin-9 in interaction between L. major and host cells. J Biol Chem. 2003;25:22223–30.CrossRefGoogle Scholar
  43. 43.
    Butschi A, Titz A, Walti MA, Olieric V, Paschinger K, Nobauer K, et al. Caenorhabditis elegans N-glycan core beta-galactoside confers sensitivity towards nematotoxic fungal galectin CGL2. PLoS Pathog. 2010;1:e1000717.CrossRefGoogle Scholar
  44. 44.
    Antia R, Ganusov VV, Ahmed R. The role of models in understanding CD8+ T-cell memory. Nat Rev Immunol. 2005;2:101–11.CrossRefGoogle Scholar
  45. 45.
    Strasser A, O’Connor L, Dixit VM. Apoptosis signaling. Annu Rev Biochem. 2000;69:217–45.PubMedCrossRefGoogle Scholar
  46. 46.
    Jackson CE, Fischer RE, Hsu AP, Anderson SM, Choi Y, Wang J, et al. Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance. Am J Hum Genet. 1999;4:1002–14.CrossRefGoogle Scholar
  47. 47.
    Kwon SW, Procter J, Dale JK, Straus SE, Stroncek DF. Neutrophil and platelet antibodies in autoimmune lymphoproliferative syndrome. Vox Sang. 2003;4:307–12.CrossRefGoogle Scholar
  48. 48.
    Fecho K, Bentley SA, Cohen PL. Mice deficient in Fas ligand (gld) or Fas (lpr) show few alterations in granulopoiesis. Cell Immunol. 1998;188:19–32.PubMedCrossRefGoogle Scholar
  49. 49.
    Fecho K, Cohen PL. Fas ligand (gld)- and Fas (lpr)-deficient mice do not show alterations in the extravasation or apoptosis of inflammatory neutrophils. J Leukoc Biol. 1998;64:373–83.PubMedGoogle Scholar
  50. 50.
    Lagasse E, Weissman IL. Bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. J Exp Med. 1994;179:1047–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Shi J, Gilbert GE, Kokubo Y, Ohashi T. Role of the liver in regulating numbers of circulating neutrophils. Blood. 2001;98:1226–30.PubMedCrossRefGoogle Scholar
  52. 52.
    Schlegel RA, Williamson P. Phosphatidylserine, a death knell. Cell Death Differ. 2001;8:551–63.PubMedCrossRefGoogle Scholar
  53. 53.
    Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature. 2000;405:85–90.PubMedCrossRefGoogle Scholar
  54. 54.
    Stowell SR, Cho M, Feasley CL, Arthur CM, Song X, Colucci JK, et al. Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing dimer formation. J Biol Chem. 2009;284:4989–99.PubMedCrossRefGoogle Scholar
  55. 55.
    Dias-Baruffi M, Zhu H, Cho M, Karmakar S, McEver RP, Cummings RD. Dimeric galectin-1 induces surface exposure of phosphatidylserine and phagocytic recognition of leukocytes without inducing apoptosis. J Biol Chem. 2003;278:41282–93.PubMedCrossRefGoogle Scholar
  56. 56.
    Stowell SR, Karmakar S, Arthur CM, Ju T, Rodrigues LC, Riul TB, et al. Galectin-1 induces reversible phosphatidylserine exposure at the plasma membrane. Mol Biol Cell. 2009;20:1408–18.PubMedCrossRefGoogle Scholar
  57. 57.
    Stowell SR, Karmakar S, Stowell CJ, Dias-Baruffi M, McEver RP, Cummings RD. Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells. Blood. 2007;109:219–27.PubMedCrossRefGoogle Scholar
  58. 58.
    Karlsson A, Christenson K, Matlak M, Bjorstad A, Brown KL, Telemo E, et al. Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils. Glycobiology. 2009;19:16–20.PubMedCrossRefGoogle Scholar
  59. 59.
    Stowell SR, Qian Y, Karmakar S, Koyama NS, Dias-Baruffi M, Leffler H, et al. Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol. 2008;180:3091–102.PubMedGoogle Scholar
  60. 60.
    Woodfin A, Voisin MB, Nourshargh S. Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol. 2010;17:9–17.PubMedCrossRefGoogle Scholar
  61. 61.
    Johnston GI, Cook RG, McEver RP. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989;56:1033–44.PubMedCrossRefGoogle Scholar
  62. 62.
    Cooper D, Norling LV, Perretti M. Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. J Leukoc Biol. 2008;83:1459–66.PubMedCrossRefGoogle Scholar
  63. 63.
    La M, Cao TV, Cerchiaro G, Chilton K, Hirabayashi J, Kasai K, et al. A novel biological activity for galectin-1: inhibition of leukocyte-endothelial cell interactions in experimental inflammation. Am J Pathol. 2003;163:1505–15.PubMedCrossRefGoogle Scholar
  64. 64.
    Sato S, Ouellet N, Pelletier I, Simard M, Rancourt A, Bergeron MG. Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol. 2002;168:1813–22.PubMedGoogle Scholar
  65. 65.
    Nieminen J, St-Pierre C, Bhaumik P, Poirier F, Sato S. Role of galectin-3 in leukocyte recruitment in a murine model of lung infection by Streptococcus pneumoniae. J Immunol. 2008;180:2466–73.PubMedGoogle Scholar
  66. 66.
    Karlsson A, Follin P, Leffler H, Dahlgren C. Galectin-3 activates the NADPH-oxidase in exudated but not peripheral blood neutrophils. Blood. 1998;91:3430–8.PubMedGoogle Scholar
  67. 67.
    Parkos CA, Dinauer MC, Jesaitis AJ, Orkin SH, Curnutte JT. Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease. Blood. 1989;73:1416–20.PubMedGoogle Scholar
  68. 68.
    Fernandez GC, Ilarregui JM, Rubel CJ, Toscano MA, Gomez SA, Bompadre MB, et al. Galectin-3 and soluble fibrinogen act in concert to modulate neutrophil activation and survival. Involvement of alternative MAPK-pathways. Glycobiology. 2004;15:519–27.PubMedCrossRefGoogle Scholar
  69. 69.
    Almkvist J, Faldt J, Dahlgren C, Leffler H, Karlsson A. Lipopolysaccharide-induced gelatinase granule mobilization primes neutrophils for activation by galectin-3 and formylmethionyl-Leu-Phe. Infect Immun. 2001;69:832–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Feuk-Lagerstedt E, Jordan ET, Leffler H, Dahlgren C, Karlsson A. Identification of CD66a and CD66b as the major galectin-3 receptor candidates in human neutrophils. J Immunol. 1999;163:5592–8.PubMedGoogle Scholar
  71. 71.
    Almkvist J, Dahlgren C, Leffler H, Karlsson A. Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1. J Immunol. 2002;168:4034–41.PubMedGoogle Scholar
  72. 72.
    Baum LG, Seilhamer JJ, Pang M, Levine WB, Beynon D, Berliner JA. Synthesis of an endogeneous lectin, galectin-1, by human endothelial cells is up-regulated by endothelial cell activation. Glycoconj J. 1995;12:63–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Thijssen VL, Hulsmans S, Griffioen AW. The galectin profile of the endothelium: altered expression and localization in activated and tumor endothelial cells. Am J Pathol. 2008;172:545–53.PubMedCrossRefGoogle Scholar
  74. 74.
    Dias-Baruffi M, Stowell SR, Song SC, Arthur CM, Cho M, Rodrigues LC, et al. Differential expression of immunomodulatory galectin-1 in peripheral leukocytes and adult tissues and its cytosolic organization in striated muscle. Glycobiology. 2010;20:507–20.PubMedCrossRefGoogle Scholar
  75. 75.
    Meszaros AJ, Reichner JS, Albina JE. Macrophage phagocytosis of wound neutrophils. J Leukoc Biol. 1999;65:35–42.PubMedGoogle Scholar
  76. 76.
    Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6:173–82.PubMedCrossRefGoogle Scholar
  77. 77.
    Galli SJ, Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol. 2010;40:1843–51.PubMedCrossRefGoogle Scholar
  78. 78.
    Frigeri LG, Liu FT. Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages. J Immunol. 1992;148:861–7.PubMedGoogle Scholar
  79. 79.
    Suzuki Y, Inoue T, Yoshimaru T, Ra C. Galectin-3 but not galectin-1 induces mast cell death by oxidative stress and mitochondrial permeability transition. Biochim Biophys Acta. 2008;1783:924–34.PubMedCrossRefGoogle Scholar
  80. 80.
    Rabinovich GA, Sotomayor CE, Riera CM, Bianco I, Correa SG. Evidence of a role for galectin-1 in acute inflammation. Eur J Immunol. 2000;30:1331–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Niki T, Tsutsui S, Hirose S, Aradono S, Sugimoto Y, Takeshita K, et al. Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation. J Biol Chem. 2009;284:32344–52.PubMedCrossRefGoogle Scholar
  82. 82.
    Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–69.PubMedCrossRefGoogle Scholar
  83. 83.
    Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953–64.PubMedCrossRefGoogle Scholar
  84. 84.
    Rabinovich G, Castagna L, Landa C, Riera CM, Sotomayor C. Regulated expression of a 16-kd galectin-like protein in activated rat macrophages. J Leukoc Biol. 1996;59:363–70.PubMedGoogle Scholar
  85. 85.
    Paz I, Sachse M, Dupont N, Mounier J, Cederfur C, Enninga J, et al. Galectin-3, a marker for vacuole lysis by invasive pathogens. Cell Microbiol. 2010;12:530–44.PubMedCrossRefGoogle Scholar
  86. 86.
    Correa SG, Sotomayor CE, Aoki MP, Maldonado CA, Rabinovich GA. Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages. Glycobiology. 2003;13:119–28.PubMedCrossRefGoogle Scholar
  87. 87.
    Barrionuevo P, Beigier-Bompadre M, Ilarregui JM, Toscano MA, Bianco GA, Isturiz MA, et al. A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol. 2007;178:436–45.PubMedGoogle Scholar
  88. 88.
    Zúñiga E, Gruppi A, Hirabayashi J, Kasai KI, Rabinovich GA. Regulated expression and effect of galectin-1 on Trypanosoma cruzi-infected macrophages: modulation of microbicidal activity and survival. Infect Immun. 2001;69:6804–12.PubMedCrossRefGoogle Scholar
  89. 89.
    Liu FT, Rabinovich GA. Galectins: regulators of acute and chronic inflammation. Ann NY Acad Sci. 2010;1183:158–82.PubMedCrossRefGoogle Scholar
  90. 90.
    Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol. 2000;165:2156–64.PubMedGoogle Scholar
  91. 91.
    Almkvist J, Karlsson A. Galectins as inflammatory mediators. Glycoconj J. 2004;19:575–81.PubMedCrossRefGoogle Scholar
  92. 92.
    Liu FT, Hsu DK, Zuberi RI, Kuwabara I, Chi EY, Henderson Jr WR. Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. Am J Pathol. 1995;147:1016–28.PubMedGoogle Scholar
  93. 93.
    Greenwald AG, Jin R, Waddell TK. Galectin-3-mediated xenoactivation of human monocytes. Transplantation. 2009;87:44–51.PubMedCrossRefGoogle Scholar
  94. 94.
    Rotshenker S. The role of galectin-3/MAC-2 in the activation of the innate-immune function of phagocytosis in microglia in injury and disease. J Mol Neurosci. 2009;39:99–103.PubMedCrossRefGoogle Scholar
  95. 95.
    Jeon SB, Yoon HJ, Chang CY, Koh HS, Jeon SH, Park EJ. Galectin-3 exerts cytokine-like regulatory actions through the JAK-STAT pathway. J Immunol. 2010;185:7037–46.PubMedCrossRefGoogle Scholar
  96. 96.
    MacKinnon AC, Farnworth SL, Hodkinson PS, Henderson NC, Atkinson KM, Leffler H, et al. Regulation of alternative macrophage activation by galectin-3. J Immunol. 2008;180:2650–8.PubMedGoogle Scholar
  97. 97.
    Matsura A, Tsukada J, Mizobe T, Higashi T, Mouri F, Tanikawa R, et al. Intracellular galectin-9 activates inflammatory cytokines in monocytes. Genes Cells. 2009;14:511–21.CrossRefGoogle Scholar
  98. 98.
    Jayaraman P, Sada-Ovalle I, Beladi S, Anderson AC, Dardalhon V, Hotta C, et al. Tim3 binding to galectin-9 stimulates antimicrobial immunity. J Exp Med. 2010;207:2343–54.PubMedCrossRefGoogle Scholar
  99. 99.
    Steinman RM. Dendritic cells: understanding immunogenicity. Eur J Immunol. 2007;37:53–60.CrossRefGoogle Scholar
  100. 100.
    Agrawal A, Agrawal S, Tay J, Gupta S. Biology of dendritic cells in aging. J Clin Immunol. 2008;28:14–20.PubMedCrossRefGoogle Scholar
  101. 101.
    Ilarregui JM, Rabinovich GA. Tolerogenic dendritic cells in the control of autoimmune neuroinflammation: an emerging role of protein-glycan interactions. Neuroimmunomodulation. 2010;17:157–60.PubMedCrossRefGoogle Scholar
  102. 102.
    Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2007;25:267–96.PubMedCrossRefGoogle Scholar
  103. 103.
    Blois SM, Ilarregui JM, Tometten M, Garcia M, Orsal AS, Cordo-Russo R, et al. A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med. 2007;13:1450–7.PubMedCrossRefGoogle Scholar
  104. 104.
    Fulcher JA, Chang MH, Wang S, Almazan T, Hashimi ST, Eriksson AU, et al. Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. J Biol Chem. 2009;284:26860–70.PubMedCrossRefGoogle Scholar
  105. 105.
    Saegusa J, Hsu DK, Chen HY, Yu L, Fermin A, Fung MA, et al. Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis. Am J Pathol. 2009;174:922–31.PubMedCrossRefGoogle Scholar
  106. 106.
    Breuilh L, Vanhoutte F, Fontaine J, van Stijn CM, Tillie-Leblond I, Capron M, et al. Galectin-3 modulates immune and inflammatory responses during helminthic infection: impact of galectin-3 deficiency on the functions of dendritic cells. Infect Immun. 2007;75:5148–57.PubMedCrossRefGoogle Scholar
  107. 107.
    Hsu DK, Chernyavsky AI, Chen HY, Yu L, Grando SA, Liu FT. Endogenous galectin-3 is localized in membrane lipid rafts and regulates migration of dendritic cells. J Invest Dermatol. 2009;129:573–83.CrossRefGoogle Scholar
  108. 108.
    Dai SY, Nakagawa R, Itoh A, Murakami H, Kashio Y, Abe H, et al. Galectin-9 induces maturation of human monocyte-derived dendritic cells. J Immunol. 2005;175:2974–81.PubMedGoogle Scholar
  109. 109.
    Bax M, García-Vallejo JJ, Jang-Lee J, North SJ, Gilmartin TJ, Hernández G, et al. Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins. J Immunol. 2007;179:8216–24.PubMedGoogle Scholar
  110. 110.
    Suk K, Hwang DY, Lee MS. Natural autoantibody to galectin-9 in normal human sera. J Clin Immunol. 1999;19:158–65.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Juan P. Cerliani
    • 1
  • Sean R. Stowell
    • 2
  • Iván D. Mascanfroni
    • 1
  • Connie M. Arthur
    • 2
  • Richard D. Cummings
    • 2
  • Gabriel A. Rabinovich
    • 1
  1. 1.Laboratorio de Inmunopatología, Instituto de Biología y Medicina ExperimentalConsejo Nacional de Investigaciones Científicas y TécnicasBuenos AiresArgentina
  2. 2.Department of BiochemistryEmory University School of MedicineAtlantaUSA

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