Browse > Article
http://dx.doi.org/10.4062/biomolther.2012.20.5.433

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)
Publication Information
Biomolecules & Therapeutics / v.20, no.5, 2012 , pp. 433-445 More about this Journal
Abstract
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.
Keywords
${\beta}$-Glucan; Triple helix; Dectin-1; Toll-like receptor (TLR); Peyer's patch; Signal transduction;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 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.   DOI   ScienceOn
2 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.   DOI
3 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.   DOI
4 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.   DOI
5 Brown, G. D. and Gordon, S. (2001) Immune recognition. A new receptor for ${\beta}$-glucans. Nature 413, 36-37.
6 Brown, G. D. (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6, 33-43.   DOI   ScienceOn
7 Brown, G. D. (2011) Innate antifungal immunity, the key role of phagocytes. Annu. Rev. Immunol. 29, 1-21.   DOI
8 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.   DOI
9 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.   DOI   ScienceOn
10 Chihara, G., Hamuro, J., Maeda, Y., Arai, Y. and Fukuoka, F. (1970) Antitumour polysaccharide derived chemically from natural glucan (Pachyman). Nature 225, 943-944.   DOI   ScienceOn
11 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.   DOI
12 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.   DOI
13 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.   DOI
14 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.   DOI
15 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.   DOI
16 Di Carlo, F. J. and Fiore, J. V. (1958) On the composition of zymosan. Science 127, 756-757.
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.   DOI
21 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.   DOI
22 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.   DOI
23 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.   DOI
24 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.   DOI
25 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.
26 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.   DOI   ScienceOn
27 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.   DOI
28 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.   DOI   ScienceOn
29 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.   DOI
30 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.   DOI
31 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.   DOI   ScienceOn
32 Goodridge, H. S., Underhill, D. M. and Touret, N. (2012) Mechanisms of Fc receptor and dectin-1 activation for phagocytosis. Traffic 13, 1062-1071.   DOI
33 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.   DOI   ScienceOn
34 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.   DOI
35 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.   DOI
36 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.   DOI
37 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.
38 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.   DOI
39 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.   DOI
40 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.
41 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.   DOI
42 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.   DOI
43 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.   DOI
44 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.   DOI
45 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.   DOI
46 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.   DOI
47 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.   DOI   ScienceOn
48 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.   DOI
49 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.   DOI
50 Kidd, P. M. (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern. Med. Rev. 5, 4-27.
51 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.   DOI
52 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.   DOI
53 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.   DOI
54 Kodama, N., Komuta, K. and Nanba, H. (2002) Can maitake MD-fraction aid cancer patients? Altern. Med. Rev. 7, 236-239.
55 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.   DOI
56 Macpherson, A. J. and Harris, N. L. (2004) Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478-485.   DOI
57 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.   DOI   ScienceOn
58 Lamkanfi, M., Malireddi, R. K. and Kanneganti, T. D. (2009) Fungal zymosan and mannan activate the cryopyrin inflammasome. J. Biol. Chem. 284, 20574-20581.   DOI   ScienceOn
59 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.   DOI
60 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.   DOI
61 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.   DOI
62 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.   DOI
63 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.   DOI
64 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.   DOI
65 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.
66 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.   DOI   ScienceOn
67 Nanba, H., Kodama, N., Schar, D. and Turner, D. (2000) Effects of maitake (Grifola frondosa) glucan in HIV-infected patients. Mycoscience 41, 293-295.   DOI   ScienceOn
68 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.   DOI
69 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.   DOI
70 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.   DOI
71 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.
72 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.
73 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.   DOI
74 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.   DOI
75 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.   DOI
76 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.   DOI
77 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.
78 Reid, D. M., Gow, N. A. and Brown, G. D. (2009) Pattern recognition: recent insights from dectin-1. Curr. Opin. Immunol. 21, 30-37.   DOI
79 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.   DOI
80 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.   DOI
81 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.   DOI   ScienceOn
82 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.   DOI   ScienceOn
83 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.   DOI
84 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.   DOI
85 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.   DOI
86 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.   DOI
87 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.   DOI
88 Saijo, S. and Iwakura, Y. (2011) Dectin-1 and dectin-2 in innate immunity against fungi. Int. Immunol. 23, 467-472.   DOI
89 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.   DOI
90 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.   DOI   ScienceOn
91 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.
92 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.   DOI
93 Sun, L. and Zhao, Y. (2007) The biological role of dectin-1 in immune response. Int. Rev. Immunol. 26, 349-364.   DOI
94 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.
95 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.   DOI
96 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.   DOI
97 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.   DOI
98 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.
99 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.   DOI
100 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.   DOI
101 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.   DOI   ScienceOn
102 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.   DOI
103 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.   DOI
104 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.   DOI
105 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.   DOI   ScienceOn
106 Volman, J. J., Ramakers, J. D. and Plat, J. (2008) Dietary modulation of immune function by ${\beta}$-glucans. Physiol. Behav. 94, 276-284.   DOI
107 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.   DOI
108 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.   DOI
109 Wang, X. and Zhang, L. (2009) Physicochemical properties and antitumor activities for sulfated derivatives of lentinan. Carbohydr. Res. 344, 2209-2216.   DOI
110 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.   DOI
111 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.   DOI
112 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.   DOI   ScienceOn
113 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.
114 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.   DOI
115 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.   DOI
116 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.
117 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.   DOI
118 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.   DOI
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.   DOI
120 Zhang, X., Zhang, L. and Xu, X. (2004) Morphologies and conformation transition of lentinan in aqueous NaOH solution. Biopolymers 75, 187-195.   DOI   ScienceOn
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.   DOI   ScienceOn
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.   DOI
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.   DOI