Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1

  • Batbayar, Sainkhuu (Department of Life Sciences, BK21 Cellular Stress Team, University of Seoul) ;
  • Lee, Dong-Hee (Department of Life Sciences, BK21 Cellular Stress Team, University of Seoul) ;
  • Kim, Ha-Won (Department of Life Sciences, BK21 Cellular Stress Team, University of Seoul)
  • Received : 2012.09.11
  • Accepted : 2012.09.19
  • Published : 2012.09.30


During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. ${\beta}$-Glucans are glucose polymers of a linear ${\beta}$(1,3)-glucan backbone with ${\beta}$(1,6)-linked side chains. The immunostimulatory and antitumor activities of ${\beta}$-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate ${\beta}$-glucans, despite their large size, can be taken up by the M cells of Peyer's patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled ${\beta}$-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of ${\beta}$-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of ${\beta}$-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of ${\beta}$-glucan contributes to its immunostimulating effect in hosts and the potential uses of ${\beta}$-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of ${\beta}$-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.



Supported by : Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF)


  1. Alvarez, Y., Valera, I., Municio, C., Hugo, E., Padron, F., Blanco, L., Rodriguez, M. Fernandez, N. and Crespo, A. S. (2010) Eicosanoids in the innate immune response, TLR and non-TLR routes. Mediator Inflamm. doi, 10.1155/2010/201929.
  2. Bae, A. H., Lee, S. W., Ikeda, M., Sano, M, Shinkai, S. and Sakurai, K. (2004) Rod-like architecture and helicity of the poly(C)/schizophyllan complex observed by AFM and SEM. Carbohyd. Res. 339, 251-258.
  3. Bae, S. H., Kim, B. R., Kang, B. J., Tsutsui, N., Okutsu, T., Shinji, J., Jang, I. K., Han, C. H. and Wilder, M. N. (2012) Molecular coloning of prophenoloxidase and the effects of dietary ${\beta}$-glucan and rutin on immune response in hemocytes of the fleshy shrimp, Fenneropenaeus chinensis. Fish Shellfish Immunol. 33, 597-604.
  4. Batbayar, S., Kim, M. J. and Kim, H. W. (2011) Medicinal mushroom Lingzhi or Reishi, Ganoderma lucidum (W.Curt.,Fr.) P. Karst., ${\beta}$-glucan induces toll-like receptors and fails to induce inflammatory cytokines in NF-${\kappa}B$ inhibitor-treated macrophages. Int. J. Med. Mushrooms 13, 213-225.
  5. Battilana, P., Ornstein, K., Minehira, K., Schwarz, J. M., Acheson, K., Schneiter, P., Burri, J, Jequier, E. and Tappy, L. (2001) Mechanisms of action of ${\beta}$-glucan in postprandial glucose metabolism in healthy men. Eur. J. Clin. Nutr. 55, 327-333.
  6. Bergendiova, K., Tibenska, E. and Majtan, J. (2011) Pleuran (${\beta}$-glucan from Pleurotus ostreatus) supplementation, cellular immune response and respiratory tract infections in athletes. Eur. J. Appl. Physiol. 111, 2033-2040.
  7. Bobovcak M., Kuniakova, R., Gabriz, J. and Majtan, J. (2010) Effect of pleuran (${\beta}$-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes. Appl. Physiol. Nutr. Metab. 35, 755-762.
  8. Brayden, D. J., Jepson, M. A. and Baird, A. W. (2005) Keynote review, intestinal Peyer's patch M cells and oral vaccine targeting. Drug Discov. Today 10, 1145-1157.
  9. Brown, G. D. and Gordon, S. (2001) Immune recognition. A new receptor for ${\beta}$-glucans. Nature 413, 36-37.
  10. Brown, G. D. (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6, 33-43.
  11. Brown, G. D. (2011) Innate antifungal immunity, the key role of phagocytes. Annu. Rev. Immunol. 29, 1-21.
  12. Chai, L. Y., de Boer, M. G., van der Velden, W. J., Plantinga, T. S., van Spriel, A. B., Jacobs, C., Halkes, C. J., Vonk, A. G., Blijlevens, N. M., van Dissel, J. T., Donnelly, P. J., Kullberg, B. J., Maertens, J. and Netea, M. G. (2011) The Y238X stop codon polymorphism in the human ${\beta}$-glucan receptor dectin-1 and susceptibility to invasive aspergillosis. J. Infect. Dis. 203, 736-743.
  13. Chan, G. C., Chan, W. K. and Sze, D. M. (2009) The effects of ${\beta}$-glucan on human immune and cancer cells. J. Hematol. Oncol. 2, 25.
  14. Chihara, G., Hamuro, J., Maeda, Y., Arai, Y. and Fukuoka, F. (1970) Antitumour polysaccharide derived chemically from natural glucan (Pachyman). Nature 225, 943-944.
  15. Cleary, J. A., Kelly, G. E. and Husband, A. J. (1999) The effect of molecular weight and ${\beta}$-1,6-linkages on priming of macrophage function in mice by (1,3)-${\beta}$-D-glucan. Immunol. Cell Biol. 77, 395-403.
  16. Cunha, C., Di Ianni, M., Bozza, S., Giovannini, G., Zagarella, S., Zelante, T., D'Angelo, C., Pierini, A., Pitzurra, L., Falzetti, F., Carotti, A., Perruccio, K., Latge, J. P., Rodrigues, F., Velardi, A., Aversa, F., Romani, L. and Carvalho, A. (2010) Dectin-1 Y238X polymorphism associates with susceptibility to invasive aspergillosis in hematopoietic transplantation through impairment of both recipient- and donor-dependent mechanisms of antifungal immunity. Blood 116, 5394-5402.
  17. Dan, J. M., Kelly, R. M., Lee, C. K. and Levitz, S. M. (2008) Role of the mannose receptor in a murine model of Cryptococcus neoformans infection. Infect. Immun. 76, 2362-2367.
  18. del Pilar Jimenez-A, M., Viriyakosol, S., Walls, L., Datta, S. K., Kirkland, T., Heinsbroek, S. E. M., Brown, G. and Fierer, J. (2008) Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of dectin-1 (Clec7a). Genes Immun. 9, 338-348.
  19. Dennehy, K. M., Willment, J. A., Williams, D. L. and Brown, G. D. (2009) Reciprocal regulation of IL-23 and IL-12 following co-activation of dectin-1 and TLR signaling pathways. Eur. J. Immunol. 39, 1379-1386.
  20. Di Carlo, F. J. and Fiore, J. V. (1958) On the composition of zymosan. Science 127, 756-757.
  21. Donaldson, D. S., Kobayashi, A., Ohno, H., Yagita, H., Williams, I. R. and Mabbott, N. A. (2012) M cell-depletion blocks oral prion disease pathogenesis. Mucosal Immunol. 5, 216-225.
  22. Dong, S. F., Chen, J. M., Zhang, W., Sun, S. H., Wang, J., Gu, J. X., Boraschi, D. and Qu, D. (2007) Specific immune response to HBsAg is enhanced by b-glucan oligosaccharide containing an ${\alpha}-(1{\rightarrow}3)$-linked bond and biased towards M2/Th2. Int. Immunopharmacol. 7, 725-733.
  23. Drummond, R. A. and Brown, G. D. (2011) The role of dectin-1 in the host defense against fungal infections. Curr. Opin. Microbiol. 14, 392-399.
  24. Elsori, D. H., Yakubenko, V. P., Roome, T., Thiagarajan, P. S., Bhattacharjee, A., Yadav, S. P. and Cathcart, M. K. (2011) Protein kinase Cd is a critical component of dectin-1 signaling in primary human monocytes. J. Leukoc. Biol. 90, 599-611.
  25. Engstad, C. S., Engstad, R. E., Olsen, J. O. and Osterud, B. (2002) The effect of soluble ${\beta}$-1,3-glucan and lipopolysaccharide on cytokine production and coagulation activation in whole blood. Int. Immunopharmacol. 2, 1585-1597.
  26. Esteban, A., Popp, M. W., Vyas, V. K., Strijbis, K., Ploegh, H. L. and Fink, G. R. (2011) Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages. Proc. Natl. Acad. Sci. U. S. A. 108, 14270-14275.
  27. Fang, J., Wang, Y., Lv, X., Shen, X., Ni, X. and Ding, K. (2012) Structure of a ${\beta}$-glucan from Grifola frondosa and its antitumor effect by activating dectin-1/Syk/NF-${\kappa}B$ signaling. Glycoconj. J. 29, 365-377.
  28. Ferwerda, G., Netea, M. G., Joosten, L. A., van der Meer, J. W. M., Romani, L. and Kullberg, B. J. (2010) The role of toll-like receptors and C-type lectins for vaccination against Candida albicans. Vaccine 28, 614-622.
  29. Fujimoto, S., Furue, H., Kimura, T., Kondo, T., Orita, K., Taguchi, T., Yoshida, K. and Ogawa, N. (1984) Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer-a randomized controlled trial. Jpn. J. Surg. 14, 286-292.
  30. Gales, A., Conduche, A., Bernad, J., Lefevre, L., Olagnier, D., Beraud, M., Martin-Blondel, G., Linas, M. D., Auwerx, J., Coste, A. and Pipy, B. (2010) PPARg controls dectin-1 expression required for host antifungal defense against Candida albicans. PLoS Pathog. 6, e1000714.
  31. Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S. and Underhill, D. M, (2003) Collaborative induction of inflammatory responses by dectin-1 and toll-like receptor 2. J. Exp. Med. 197, 1107-1117.
  32. Gaullier, J. M., Sleboda, J., Ofjord, E. S., Ulvestad, E., Nurminiemi, M., Moe, C., Tor, A. and Gudmundsen, O. (2011) Supplementation with a soluble ${\beta}$-glucan exported from shiitake medicinal mushroom, Lentinus edodes (Berk.) Singer mycelium: a crossover, placebo-controlled study in healthy elderly. Int. J. Med. Mushrooms 13, 319-326.
  33. Gersuk, G. M., Underhill, D. M., Zhu, L. and Marr, K. A. (2006) Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J. Immunol. 176, 3717-3724.
  34. Gitik, M., Reichert, F. and Rotshenker, S. (2010) Cytoskeleton plays a dual role of activation and inhibition in myelin and zymosan phagocytosis by microglia. FASEB J. 24, 2211-2221.
  35. Goodridge, H. S., Reyes, C. N., Becker, C. A., Katsumoto, T. R., Ma, J., Wolf, A. J., Bose, N., Chan, A. S., Magee, A. S., Danielson, M. E., Weiss, A., Vasilakos, J. P. and Underhill, D. M. (2011) Activation of the innate immune receptor dectin-1 upon formation of a 'phagocytic synapse'. Nature 472, 471-475.
  36. Goodridge, H. S., Underhill, D. M. and Touret, N. (2012) Mechanisms of Fc receptor and dectin-1 activation for phagocytosis. Traffic 13, 1062-1071.
  37. Greenblatt, M. B., Aliprantis, A., Hu, B. and Glimcher, L. H. (2010) Calcineurin regulates innate antifungal immunity in neutrophils. J. Exp. Med. 207, 923-931.
  38. Gringhuis, S. I., Wevers, B. A., Kaptein, T. M., van Capel, T. M. M., Theelen, B., Boekhout, T., de Jong, E. C. and Geijtenbeek, T. B. (2011) Selective C-Rel activation via Malt1 controls anti-fungal $T_H-17$ immunity by dectin-1 and dectin-2. PLoS Pathog. 7, e1001259.
  39. Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschlager, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V., Mocsai, A., Tschopp, J. and Ruland, J. (2009) Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459, 433-436.
  40. Gu, Y. H., Takagi, Y., Nakamura, T., Hasegawa, T., Suzuki, I., Oshima, M., Tawaraya, H. and Niwano, Y. (2005) Enhancement of radioprotection and anti-tumor immunity by yeast-derived ${\beta}$-glucan in mice. J. Med. Food 8, 154-158.
  41. Hayakawa, K., Mitsuhashi, N., Saito, Y., Takahashi, M., Katano, S., Shiojima, K., Furuta, M. and Niibe, H. (1993) Effect of Krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. Anticancer Res. 13, 1815-1820.
  42. Heinsbroek, S. E., Oei, A., Roelofs, J. J, Dhawan, S., te Velde, A. Gordon, S. and de Jonge, W. J. (2012) Genetic deletion of dectin-1 does not affect the course of murine experimental colitis. BMC Gastroenterol. 12, 33.
  43. Hino, S., Kito, A., Yokoshima, R., Sugino, R., Oshima, K., Morita, T., Okajima, T., Nadano, D., Uchida, K. and Matsuda, T. (2012) Discharge of solubilized and dectin-1-reactive b-glucan from macrophage cells phagocytizing insoluble b-glucan particles: involvement of reactive oxygen species (ROS)-driven degradation. Biochem. Biophys. Res. Commun. 421, 329-334.
  44. Huang, H., Ostroff, G. R., Lee, C. K., Specht, C. A. and Levitz, S. M. (2010) Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded ${\beta}$-glucan particles. MBio 1, e00164-10.
  45. Huang, H., Ostroff, G. R., Lee, C. K., Agarwal, S., Ram, S., Rice, P. A., Specht, C. A. and Levitz, S. M. (2012) Relative contributions of dectin-1 and complement to immune responses to particulate ${\beta}$-glucans. J. Immunol. 189, 312-317.
  46. Hughes, C. E., Pollitt, A. Y., Mori, J., Eble, J. A., Tomlinson, M. G., Hartwig, J. H., O'Callaghan, C. A., Futterer, K. and Watson, S. P. (2010) CLEC-2 activates Syk through dimerization. Blood 115, 2947-2955.
  47. Iliev, I. D., Funari, V. A., Taylor, K. D., Nguyen, Q., Reyes, C. N., Strom, S. P., Brown, J., Becker, C. A., Fleshner, P. R., Dubinsky, M., Rotter, J. I., Wang, H. L., McGovern, D. P., Brown, G. D. and Underhill D. M. (2012) Interactions between commensal fungi and the C-type lectin receptor dectin-1 influence colitis. Science 336, 1314-1317.
  48. Ishibashi, K., Miura, N. N., Adachi, Y., Ohno, N. and Yadomae, T. (2001) Relationship between solubility of grifolan, a fungal 1,3-${\beta}$-D-glucan, and production of tumor necrosis factor by macrophages in vitro. Biosci. Biotechnol. Biochem. 65, 1993-2000.
  49. Kankkunen, P., Teirilä, L., Rintahaka, J., Alenius, H., Wolff, H. and Matikainen, S. (2010) (1,3) ${\beta}$-Glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J. Immunol. 184, 6335-6342.
  50. Karacsonyi, S. and Kuniak, L. (1994) Polysaccharides of Pleurotus ostreatus: isolation and structure of pleuran, an alkali-insoluble ${\beta}$-D-glucan. Carbohydr. Polym. 24, 107-111.
  51. Kerneis, S., Bogdanova, A., Kraehenbuhl, J. P. and Pringault, E. (1997) Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277, 949-952.
  52. Kerrigan, A. M. and Brown, G. D. (2010) Syk-coupled C-type lectin receptors that mediate cellular activation via single tyrosine based activation motifs. Immunol. Rev. 234, 335-352.
  53. Kidd, P. M. (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern. Med. Rev. 5, 4-27.
  54. Kim, S. I., Park, H. G., Cho, G. H., Ko, I. S. and Kim, H. W. (2009) Cooperative effect of the lipopolysaccharide and culinary-medicinal cauliflower mushroom Sparassis crispa (Wulf.) Fr. (Aphyllophoromycetideae)-derived ${\beta}$-glucan on inflammatory cytokine secretion by the murine macrophage cell line. Int. J. Med. Mushrooms 11, 9-20.
  55. Kim, H. S., Kim, J. Y., Lee, H. K., Kim, M. S., Lee, S. R., Kang, J. S., Kim, H. M., Lee, K. A., Hong, J. T., Kim, Y. and Han, S. B. (2010) Dendritic cell activation by glucan isolated from Umbilicaria esculenta. Immune Netw. 10, 188-197.
  56. Kobayashi, T., Kawamura, H., Kanda, Y., Matsumoto, H., Saito, S., Takeda, K., Kawamura, T. and Abo, T. (2012) Natural killer T cells suppress zymosan A-mediated granuloma formation in the liver by modulating interferon-$\gamma$ and interleukin-10. Immunol. 136, 86-95.
  57. Kock, G., Bringmann, A., Held, S. A., Daecke, S., Heine, A. and Brossart, P. (2011) Regulation of dectin-1-mediated dendritic cell activation by peroxisome proliferator-activated receptor-gamma ligand troglitazone. Blood 117, 3569-3574.
  58. Kodama, N., Komuta, K. and Nanba, H. (2002) Can maitake MD-fraction aid cancer patients? Altern. Med. Rev. 7, 236-239.
  59. Kumar, H., Kumagai, Y., Tsuchida, T., Koenig, P. A., Satoh, T., Guo, Z., Jang, M. H., Saitoh, T., Akira, S. and Kawai, T. (2009) Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal ${\beta}$-glucan. J. Immunol. 183, 8061-8067.
  60. Kurashige, S., Akuzawa, Y. and Endo, F. (1997) Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine. Immunopharmacol. Immunotoxicol. 19, 175-183.
  61. Lamkanfi, M., Malireddi, R. K. and Kanneganti, T. D. (2009) Fungal zymosan and mannan activate the cryopyrin inflammasome. J. Biol. Chem. 284, 20574-20581.
  62. Lee, H. M., Yuk, J. M., Shin, D. M. and Jo, E. K. (2009) Dectin-1 is inducible and plays an essential role for Mycobacteria-induced innate immune responses in airway epithelial cells. J. Clin. Immunol. 29, 795-805.
  63. Macpherson, A. J. and Harris, N. L. (2004) Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478-485.
  64. Mahauthaman, R., Howell, C. J., Spur, B. W., Youlten, L. J., Clark, T. J., Lessof, M. H. and Lee, T. H. (1988) The generation and cellular distribution of leukotriene C4 in human eosinophils stimulated by unopsonized zymosan and glucan particles. J. Allergy Clin. Immunol. 81, 696-705.
  65. Masuda, Y., Togo, T., Mizuno, S., Konishi, M. and Nanba, H. (2012) Soluble ${\beta}$-glucan from Grifola frondosa induces proliferation and dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway. J. Leukoc. Biol. 91, 547-556.
  66. Mocsai, A., Ruland, J. and Tybulewicz, V. L. (2010) The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat. Rev. Immunol. 10, 387-402.
  67. Muta, T. (2006) Molecular basis for invertebrate innate immune recognition of $(1{\rightarrow}3)-{\beta}$-D-glucan as a pathogen-associated molecular pattern. Curr. Pharm. Des. 12, 4155-4161.
  68. Nakano, H., Namatame, K., Nemoto, H., Motohashi, H., Nishiyama, K. and Kumada, K. (1999) A multi-institutional prospective study of lentinan in advanced gastric cancer patients with unresectable and recurrent diseases: effect on prolongation of survival and improvement of quality of life. Kanagawa Lentinan Research Group. Hepatogastroenterol. 46, 2662-2668.
  69. Nakazato, H., Koike, A., Saji, S., Ogawa, N. and Sakamoto, J. (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 343, 1122-1126.
  70. Nanba, H., Kodama, N., Schar, D. and Turner, D. (2000) Effects of maitake (Grifola frondosa) glucan in HIV-infected patients. Mycoscience 41, 293-295.
  71. Ng, M. L. and Yap, A. T. (2002). Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes). J. Altern. Complement. Med. 8, 581-589.
  72. Ohno, N., Hashimoto, T., Adachi, Y. and Yadomae, T. (1996) Conformation dependency of nitric oxide synthesis of murine peritoneal macrophages by ${\beta}$-glucans in vitro. Immunol. Lett. 52, 157-163.
  73. Okamura, K., Suzuki, M., Chihara, T., Fujiwara, A., Fukuda, T., Goto, S., Ichinohe, K., Jimi, S., Kasamatsu, T., Kawai, N., Mizuguchi, K., Mori, S., Nakano, H., Noda, K., Sekiba, K., Suzuki, K., Suzuki, T., Takahashi, K., Takeuchi, K., Takeuchi, S. and Ogawa, N. (1986) Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer. A randomized controlled study. Cancer 58, 865-872.<865::AID-CNCR2820580411>3.0.CO;2-S
  74. Okazaki, M., Adachi, Y., Ohno, N. and Yadomae, T. (1995) Structure-activity relationship of $(1{\rightarrow}3)-{\beta}$-D-glucans in the induction of cytokine production from macrophages, in vitro. Biol. Pharm. Bull. 18, 1320-1327.
  75. Onderdonk, A. B., Cisneros, R. L., Hinkson, P. and Ostroff, G. (1992) Anti-infective effect of poly-${\beta}$ 1-6-glucotriosyl-${\beta}$ 1-3-glucopyranose glucan in vivo. Infect. Immun. 60, 1642-1647.
  76. Owen, R. L. (1999) Uptake and transport of intestinal macromolecules and microorganisms by M cells in Peyer's patches - a personal and historical perspective. Semin. Immunol. 11, 157-163.
  77. Palleschi, A., Bocchinfuso, G., Coviello, T. and Alhaique, F. (2005) Molecular dynamics investigations of the polysaccharide scleroglucan: first study on the triple helix structure. Carbohydr. Res. 340, 2154-2162.
  78. Perez-Garcia, L. A., Diaz-Jimenez, D. F., Lopez-Esparza, A. and Mora-Montes, H. M. (2011) Role of cell wall polysaccharides during recognition of Candida albicans by the innate immune system. J. Glycobiol. 1, 102.
  79. Pietrella, D., Rachini, A., Torosantucci, A., Chiani, P., Brown, A. J., Bistoni, F., Costantino, P., Mosci, P., d'Enfert, C., Rappuoli, R., Cassone, A. and Vecchiarelli, A. (2010) A ${\beta}$-glucan-conjugate vaccine and anti-b-glucan antibodies are effective against murine vaginal candidiasis as assessed by a novel in vivo imaging technique. Vaccine 28, 1717-1725.
  80. Plantinga, T. S., van der Velden, W. J., Ferwerda, B., van Spriel, A. B., Adema, G., Feuth, T., Donnelly, J. P., Brown, G. D., Kullberg, B. J, Blijlevens, N. M. and Netea, M. G. (2009) Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 49, 724-732.
  81. Pretus, H. A., Ensley, H. E., McNamee, R. B., Jones, E. L., Browder, I. W. and Williams, D. L. (1991) Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan. J. Pharmacol. Exp. Ther. 257, 500-510.
  82. Qi, C., Cai, Y., Gunn, L., Ding, C., Li, B., Kloecker, G., Qian, K., Vasilakos, J., Saijo, S., Iwakura, Y., Yannelli, J. R. and Yan, J. (2011) Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived ${\beta}$-glucans. Blood 117, 6825-6836.
  83. Rand, T. G., Sun, M., Gilyan, A., Downey, J. and Miller, J. D. (2010) Dectin-1 and inflammation-associated gene transcription and expression in mouse lungs by a toxic (1,3)-${\beta}$-D glucan. Arch. Toxicol. 84, 205-220.
  84. Reid, D. M., Gow, N. A. and Brown, G. D. (2009) Pattern recognition: recent insights from dectin-1. Curr. Opin. Immunol. 21, 30-37.
  85. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J. P. and Ricciardi-Castagnoli, P. (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361-367.
  86. Rice, P. J., Adams, E. L., Ozment-Skelton, T., Gonzalez, A. J., Goldman, M. P., Lockhart, B. E., Barker, L. A., Breuel, K. F., Deponti, W. K., Kalbfleisch, J. H., Ensley, H. E., Brown, G. D., Gordon, S. and Williams, D. L. (2005) Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J. Pharmacol. Exp. Ther. 314, 1079-1086.
  87. Rivera, A., Hohl, T. M., Collins, N., Leiner, I., Gallegos, A., Saijo, S., Coward, J. W., Iwakura, Y. and Pamer, E. G. (2011) Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation. J. Exp. Med. 208, 369-381.
  88. Roy, S., Dickerson, R., Khanna, S., Collard, E., Gnyawali, U., Gordillo, G. M. and Sen, C. K. (2011) Particulate b-glucan induces TNF-${\alpha}$ production in wound macrophages via a redox-sensitive NF- {\kappa}B$-dependent pathway. Wound Repair Regen. 19, 411-419.
  89. Said-Sadier, N., Padilla, E., Langsley, G. and Ojcius, D. M, (2010) Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5, e10008.
  90. Saijo, S., Ikeda, S., Yamabe, K., Kakuta, S., Ishigame, H., Akitsu, A., Fujikado, N., Kusaka, T., Kubo, S., Chung, S. H., Komatsu, R., Miura, N., Adachi, Y., Ohno, N., Shibuya, K., Yamamoto, N., Kawakami, K., Yamasaki, S., Saito, T., Akira, S. and Iwakura, Y. (2010) Dectin-2 recognition of a-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32, 681-691.
  91. Saijo, S. and Iwakura, Y. (2011) Dectin-1 and dectin-2 in innate immunity against fungi. Int. Immunol. 23, 467-472.
  92. Sakurai, T., Hashimoto, K., Suzuki, I., Ohno, N., Oikawa, S., Masuda, A. and Yadomae, T. (1992) Enhancement of murine alveolar macrophage functions by orally administered ${\beta}$-glucan. Int. J. Immunopharmacol. 14, 821-830.
  93. Sandvik, A., Wang, Y. Y., Morton, H. C., Aasen, A. O., Wang, J. E. and Johansen, F. E. (2007) Oral and systemic administration of ${\beta}$-glucan protects against lipopolysaccharide-induced shock and organ injury in rats. Clin. Exp. Immunol. 148, 168-177.
  94. Sasaki, T. and Takasuka, N. (1976) Further study of the structure of lentinan, an anti-tumor polysaccharide from Lentinus edodes. Carbohydr. Res. 47, 99-104.
  95. Schappi, M., Deffert, C., Fiette, L., Gavazzi, G., Herrmann, F., Belli, D. and Krause, K. H. (2008) Branched fungal ${\beta}$-glucans causes hyperinflammation and necrosis in phagocyte NADPH oxidase-deficient mice. J. Pathol. 214, 434-444.
  96. Serezani, C. H., Kane, S., Collins, L., Morato-Marques, M., Osterholzer, J. J. and Peters-Golden, M. (2012) Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis. J. Immunol. 189, 906-915.
  97. Shimizu, K., Watanabe, S., Watanabe, S., Matsuda, K., Suga, T., Nakazawa, S. and Shiratori, K. (2009). Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer. Hepatogastroenterol. 56, 240-244.
  98. Sobanov, Y., Bernreiter, A., Derdak, S., Mechtcheriakova, D., Schweighofer, B., Düchler, M., Kalthoff, F. and Hofer, E. (2001) A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex. Eur. J. Immunol. 31, 3493-3503.<3493::AID-IMMU3493>3.0.CO;2-9
  99. Sullivan, R., Smith, J. E. and Rowan, N. J. (2006) Medicinal mushrooms and cancer therapy: translating a traditional practice into western medicine. Perspect. Biol. Med. 49, 159-170.
  100. Sun, L. and Zhao, Y. (2007) The biological role of dectin-1 in immune response. Int. Rev. Immunol. 26, 349-364.
  101. Taylor, P. R., Tsoni, S. V., Willment, J. A., Dennehy, K. M., Rosas, M., Findon, H., Haynes, K., Steele, C., Botto, M., Gordon, S. and Brown, G. D. (2007) Dectin-1 is required for b-glucan recognition and control of fungal infection. Nat. Immunol. 8, 31-38.
  102. Thornton, B. P., Vetvicka, V., Pitman, M., Goldman, R. C. and Ross, G. D. (1996) Analysis of the sugar specificity and molecular location of the ${\beta}$-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J. Immunol. 156, 1235-1246.
  103. Tian, J., Ma, J., Wang, S., Yan, J., Chen, J., Tong, J., Wu, C., Liu, Y., Ma, B., Mao, C., Jiao, Z., Shao, Q., Lu, L. and Xu, H. (2011) Increased expression of mGITRL on D2SC/1 cells by particulate ${\beta}$-glucan impairs the suppressive effect of CD4+CD25+ regulatory T cells and enhances the effector T cell proliferation. Cell. Immunol. 270, 183-187.
  104. Torisu, M., Hayashi, Y., Ishimitsu, T., Fujimura, T., Iwasaki, K., Katano, M., Yamamoto, H., Kimura, Y., Takesue, M., Kondo, M. and Nomoto, K. (1990) Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol. Immunother. 31, 261-268.
  105. Torosantucci, A., Bromuro, C., Chiani, P., De Bernardis, F., Berti, F., Galli, C., Norelli, F., Bellucci, C., Polonelli, L., Costantino, P., Rappuoli, R. and Cassone, A. (2005) A novel glyco-conjugate vaccine against fungal pathogens. J. Exp. Med. 202, 597-606.
  106. Underhill, D. M., Rossnagle, E., Lowell, C. A. and Simmons, R. M. (2005) Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 106, 2543-2550.
  107. van Bruggen, R., Drewniak, A., Jansen M., van Houdt, M., Roos, D., Chapel, H., Verhoeven, A. J. and Kuijpers, T. W. (2009) Complement receptor 3, not dectin-1, is the major receptor on human neutrophils for ${\beta}$-glucan-bearing particles. Mol. Immunol. 47, 575-581.
  108. van der Velden, W. J., Plantinga, T. S., Feuth, T., Donnelly, J. P., Netea, M. G. and Blijlevens, N. M. (2010) The incidence of acute graft versus-host disease increases with Candida colonization depending the dectin-1 gene status. Clin. Immunol. 136, 302-306.
  109. Viriyakosol, S., Fierer, J., Brown, G. D. and Kirkland, T. N. (2005) Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on toll-like receptor 2 and dectin-1. Infect. Immun. 73, 1553-1560.
  110. Volman, J. J., Ramakers, J. D. and Plat, J. (2008) Dietary modulation of immune function by ${\beta}$-glucans. Physiol. Behav. 94, 276-284.
  111. Vos, A. P., M'Rabet, L., Stahl, B., Boehm, G. and Garssen, J. (2007) Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates. Crit. Rev. Immunol. 27, 97-140.
  112. Wang, X. and Zhang, L. (2009) Physicochemical properties and antitumor activities for sulfated derivatives of lentinan. Carbohydr. Res. 344, 2209-2216.
  113. Wolever, T. M., Gibbs, A. L., Brand-Miller, J., Duncan, A. M., Hart, V., Lamarche, B., Tosh, S. M. and Duss, R. (2011) Bioactive oat ${\beta}$-glucan reduces LDL cholesterol in Caucasians and non-Caucasians. Nutr. J. 10, 130.
  114. Xu, S., Huo, J., Lee K. G., Kurosaki, T. and Lam, K. P. (2009a) Phospholipase Cg2 is critical for dectin-1-mediated $Ca^{2+}$ flux and cytokine production in dendritic cells. J. Biol. Chem. 284, 7038-7046.
  115. Xu, S. L., Huo, J., Gunawan, M., Su, I. H. and Lam, K. P. (2009b) Activated dectin-1 localizes to lipid raft microdomains for signaling and activation of phagocytosis and cytokine production in dendritic cells. J. Biol. Chem. 284, 22005-22011.
  116. Yan, J., Allendorf, D. J. and Brandley, B. (2005) Yeast whole glucan particle (WGP) ${\beta}$-glucan in conjunction with antitumor monoclonal antibodies to treat cancer. Expert Opin. Biol. Ther. 5, 691-702.
  117. Yokoe, T., Iino, Y., Takei, H., Horiguchi, J., Koibuchi, Y., Maemura, M., Ohwada, S. and Morishita, Y. (1997) HLA antigen as predictive index for the outcome of breast cancer patients with adjuvant immunochemotherapy with PSK. Anticancer Res. 17, 2815-2818.
  118. Yoshiba, K., Teramoto, A., Nakamura, N., Kikuchi, K., Miyazaki, Y. and Sorai, M. (2003) Static water structure detected by heat capacity measurements on aqueous solutions of a triple-helical polysaccharide schizophyllan. Biomacromolecules 4, 1348-1356.
  119. Young, S. H., Dong, W. J. and Jacobs, R. R. (2000) Observation of a partially opened triple-helix conformation in $1{\rightarrow}3-{\beta}$-glucan by fluorescence resonance energy transfer spectroscopy. J. Biol. Chem. 275, 11874-11879.
  120. Zhang, X., Zhang, L. and Xu, X. (2004) Morphologies and conformation transition of lentinan in aqueous NaOH solution. Biopolymers 75, 187-195.
  121. Zhang, L., Li, X., Xu, X. and Zeng, F. (2005) Correlation between antitumor activity, molecular weight, and conformation of lentinan. Carbohydr. Res. 340, 1515-1521.
  122. Zhu, K., Chi, Z., Li, J., Zhang, F., Li, M., Yasoda, H. N. and Wu, L. (2006) The surface display of haemolysin from Vibrio harveyi on yeast cells and their potential applications as live vaccine in marine fish. Vaccine 24, 6046-6052.
  123. Zhu, X. and Lin, Z. (2006) Modulation of cytokines production, granzyme B and perforin in murine CIK cells by Ganoderma lucidum polysaccharides. Carbohydr. Polym. 63, 188-197.

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