DOI QR코드

DOI QR Code

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

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

References

  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. https://doi.org/10.1016/j.carres.2003.09.032
  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. https://doi.org/10.1016/j.fsi.2012.06.034
  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. https://doi.org/10.1615/IntJMedMushr.v13.i3.10
  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. https://doi.org/10.1038/sj.ejcn.1601160
  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. https://doi.org/10.1007/s00421-011-1837-z
  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. https://doi.org/10.1139/H10-070
  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. https://doi.org/10.1016/S1359-6446(05)03536-1
  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. https://doi.org/10.1038/nri1745
  11. Brown, G. D. (2011) Innate antifungal immunity, the key role of phagocytes. Annu. Rev. Immunol. 29, 1-21. https://doi.org/10.1146/annurev-immunol-030409-101229
  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. https://doi.org/10.1093/infdis/jiq102
  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. https://doi.org/10.1186/1756-8722-2-25
  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. https://doi.org/10.1038/225943a0
  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. https://doi.org/10.1046/j.1440-1711.1999.00848.x
  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. https://doi.org/10.1182/blood-2010-04-279307
  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. https://doi.org/10.1128/IAI.00095-08
  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. https://doi.org/10.1038/gene.2008.23
  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. https://doi.org/10.1002/eji.200838543
  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. https://doi.org/10.1038/mi.2011.68
  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. https://doi.org/10.1016/j.intimp.2007.01.004
  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. https://doi.org/10.1016/j.mib.2011.07.001
  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. https://doi.org/10.1189/jlb.0610376
  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. https://doi.org/10.1016/S1567-5769(02)00134-0
  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. https://doi.org/10.1073/pnas.1111415108
  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. https://doi.org/10.1007/s10719-012-9416-z
  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. https://doi.org/10.1016/j.vaccine.2009.10.082
  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. https://doi.org/10.1007/BF02469643
  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. https://doi.org/10.1371/journal.ppat.1000714
  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. https://doi.org/10.1084/jem.20021787
  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. https://doi.org/10.4049/jimmunol.176.6.3717
  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. https://doi.org/10.1096/fj.09-146118
  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. https://doi.org/10.1038/nature10071
  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. https://doi.org/10.1111/j.1600-0854.2012.01382.x
  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. https://doi.org/10.1084/jem.20092531
  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. https://doi.org/10.1371/journal.ppat.1001259
  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. https://doi.org/10.1038/nature07965
  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. https://doi.org/10.1089/jmf.2005.8.154
  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. https://doi.org/10.1186/1471-230X-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. https://doi.org/10.1016/j.bbrc.2012.04.009
  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. https://doi.org/10.4049/jimmunol.1200603
  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. https://doi.org/10.1182/blood-2009-08-237834
  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. https://doi.org/10.1126/science.1221789
  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. https://doi.org/10.1271/bbb.65.1993
  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. https://doi.org/10.4049/jimmunol.0903019
  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. https://doi.org/10.1016/0144-8617(94)90019-1
  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. https://doi.org/10.1126/science.277.5328.949
  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. https://doi.org/10.1111/j.0105-2896.2009.00882.x
  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. https://doi.org/10.1615/IntJMedMushr.v11.i1.20
  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. https://doi.org/10.4110/in.2010.10.6.188
  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. https://doi.org/10.1111/j.1365-2567.2012.03562.x
  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. https://doi.org/10.1182/blood-2010-08-302224
  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. https://doi.org/10.4049/jimmunol.0902477
  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. https://doi.org/10.3109/08923979709007657
  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. https://doi.org/10.1074/jbc.M109.023689
  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. https://doi.org/10.1007/s10875-009-9319-3
  63. Macpherson, A. J. and Harris, N. L. (2004) Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478-485. https://doi.org/10.1038/nri1373
  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. https://doi.org/10.1016/0091-6749(88)91041-X
  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. https://doi.org/10.1189/jlb.0711386
  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. https://doi.org/10.1038/nri2765
  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. https://doi.org/10.2174/138161206778743529
  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. https://doi.org/10.1016/S0140-6736(94)90233-X
  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. https://doi.org/10.1007/BF02463941
  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. https://doi.org/10.1089/107555302320825093
  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. https://doi.org/10.1016/0165-2478(96)02604-1
  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. https://doi.org/10.1002/1097-0142(19860815)58:4<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. https://doi.org/10.1248/bpb.18.1320
  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. https://doi.org/10.1006/smim.1999.0171
  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. https://doi.org/10.1016/j.carres.2005.06.026
  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. https://doi.org/10.1016/j.vaccine.2009.12.021
  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. https://doi.org/10.1086/604714
  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. https://doi.org/10.1182/blood-2011-02-339812
  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. https://doi.org/10.1007/s00204-009-0481-4
  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. https://doi.org/10.1016/j.coi.2009.01.003
  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. https://doi.org/10.1038/86373
  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. https://doi.org/10.1124/jpet.105.085415
  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. https://doi.org/10.1084/jem.20100906
  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. https://doi.org/10.1111/j.1524-475X.2011.00688.x
  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. https://doi.org/10.1371/journal.pone.0010008
  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. https://doi.org/10.1016/j.immuni.2010.05.001
  91. Saijo, S. and Iwakura, Y. (2011) Dectin-1 and dectin-2 in innate immunity against fungi. Int. Immunol. 23, 467-472. https://doi.org/10.1093/intimm/dxr046
  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. https://doi.org/10.1016/0192-0561(92)90080-5
  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. https://doi.org/10.1111/j.1365-2249.2006.03320.x
  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. https://doi.org/10.1016/S0008-6215(00)83552-1
  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. https://doi.org/10.4049/jimmunol.1200257
  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. https://doi.org/10.1002/1521-4141(200112)31:12<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. https://doi.org/10.1353/pbm.2006.0034
  100. Sun, L. and Zhao, Y. (2007) The biological role of dectin-1 in immune response. Int. Rev. Immunol. 26, 349-364. https://doi.org/10.1080/08830180701690793
  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. https://doi.org/10.1038/ni1408
  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. https://doi.org/10.1016/j.cellimm.2011.05.003
  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. https://doi.org/10.1007/BF01740932
  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. https://doi.org/10.1084/jem.20050749
  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. https://doi.org/10.1182/blood-2005-03-1239
  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. https://doi.org/10.1016/j.molimm.2009.09.018
  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. https://doi.org/10.1016/j.clim.2010.04.007
  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. https://doi.org/10.1128/IAI.73.3.1553-1560.2005
  110. Volman, J. J., Ramakers, J. D. and Plat, J. (2008) Dietary modulation of immune function by ${\beta}$-glucans. Physiol. Behav. 94, 276-284. https://doi.org/10.1016/j.physbeh.2007.11.045
  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. https://doi.org/10.1615/CritRevImmunol.v27.i2.10
  112. Wang, X. and Zhang, L. (2009) Physicochemical properties and antitumor activities for sulfated derivatives of lentinan. Carbohydr. Res. 344, 2209-2216. https://doi.org/10.1016/j.carres.2009.04.033
  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. https://doi.org/10.1186/1475-2891-10-130
  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. https://doi.org/10.1074/jbc.M806650200
  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. https://doi.org/10.1074/jbc.M109.009076
  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. https://doi.org/10.1517/14712598.5.5.691
  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. https://doi.org/10.1021/bm0300251
  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. https://doi.org/10.1074/jbc.275.16.11874
  120. Zhang, X., Zhang, L. and Xu, X. (2004) Morphologies and conformation transition of lentinan in aqueous NaOH solution. Biopolymers 75, 187-195. https://doi.org/10.1002/bip.20112
  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. https://doi.org/10.1016/j.carres.2005.02.032
  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. https://doi.org/10.1016/j.vaccine.2006.05.043
  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. https://doi.org/10.1016/j.carbpol.2005.08.002

Cited by

  1. Biaryl amide compounds reduce the inflammatory response in macrophages by regulating Dectin-1 vol.32, 2016, https://doi.org/10.1016/j.intimp.2016.01.020
  2. Antiproliferative and pro-apoptotic effects of three fungal exocellular β-glucans in MCF-7 breast cancer cells is mediated by oxidative stress, AMP-activated protein kinase (AMPK) and the Forkhead transcription factor, FOXO3a vol.67, 2015, https://doi.org/10.1016/j.biocel.2015.08.003
  3. Antioxidants of Edible Mushrooms vol.20, pp.10, 2015, https://doi.org/10.3390/molecules201019489
  4. Medicinal mushrooms: Valuable biological resources of high exploitation potential vol.151, pp.3, 2017, https://doi.org/10.1080/11263504.2017.1301590
  5. Characterization of Cell Wall α-1,3-Glucan–Deficient Mutants in Aspergillus oryzae Isolated by a Screening Method Based on Their Sensitivities to Congo Red or Lysing Enzymes vol.64, pp.3, 2017, https://doi.org/10.5458/jag.jag.JAG-2017_004
  6. Molecular Interactions of β-(1→3)-Glucans with Their Receptors vol.20, pp.6, 2015, https://doi.org/10.3390/molecules20069745
  7. Immunomodulating Activity of Aronia melanocarpa Polyphenols vol.15, pp.7, 2014, https://doi.org/10.3390/ijms150711626
  8. Effects of sulfated and non-sulfatedβ-glucan extracted fromAgaricus brasiliensisin breast adenocarcinoma cells – MCF-7 vol.25, pp.9, 2015, https://doi.org/10.3109/15376516.2015.1043762
  9. Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses vol.2014, 2014, https://doi.org/10.1155/2014/352371
  10. Extraction, characterization and biological activity of a (1,3)(1,6)-β- d -glucan from the pathogenic oomycete Pythium insidiosum vol.157, 2017, https://doi.org/10.1016/j.carbpol.2016.10.053
  11. Immunomodulatory potential of β-glucan as supportive treatment in porcine rotavirus enteritis vol.191, 2017, https://doi.org/10.1016/j.vetimm.2017.07.012
  12. The Pivotal Role of TBK1 in Inflammatory Responses Mediated by Macrophages vol.2012, 2012, https://doi.org/10.1155/2012/979105
  13. Drying enhances immunoactivity of spent brewer's yeast cell wall β-d-glucans vol.206, 2015, https://doi.org/10.1016/j.jbiotec.2015.03.024
  14. The crosstalk between Dectin1 and TLR4 via NF-κB subunits p65/RelB in mammary epithelial cells vol.23, pp.2, 2014, https://doi.org/10.1016/j.intimp.2014.09.004
  15. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro vol.11, pp.11, 2016, https://doi.org/10.1371/journal.pone.0167410
  16. Role of PTX3 in corneal epithelial innate immunity against Aspergillus fumigatus infection 2016, https://doi.org/10.1016/j.exer.2016.11.017
  17. Levan promotes antiproliferative and pro-apoptotic effects in MCF-7 breast cancer cells mediated by oxidative stress vol.102, 2017, https://doi.org/10.1016/j.ijbiomac.2017.04.035
  18. Molecular Mechanisms Associated With Particulate and Soluble Heteroglycan Mediated Immune Response vol.117, pp.7, 2016, https://doi.org/10.1002/jcb.25449
  19. Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin-1 vol.25, pp.4, 2016, https://doi.org/10.1111/exd.12931
  20. Dectin-1 agonist selectively induces IgG1 class switching by LPS-activated mouse B cells vol.178, 2016, https://doi.org/10.1016/j.imlet.2016.08.010
  21. β-(1,3)-glucan isolated from Agrobacterium species induces maturation of bone marrow-derived dendritic cells and drives Th1 immune responses vol.24, pp.4, 2015, https://doi.org/10.1007/s10068-015-0197-6
  22. Infection of Keratinocytes with Trichophytum rubrum Induces Epidermal Growth Factor-Dependent RNase 7 and Human Beta-Defensin-3 Expression vol.9, pp.4, 2014, https://doi.org/10.1371/journal.pone.0093941
  23. Orally delivered β-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation vol.35, pp.12, 2015, https://doi.org/10.1016/j.nutres.2015.09.017
  24. Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein vol.21, pp.2, 2016, https://doi.org/10.3390/molecules21020162
  25. Immune Enhancing Activity of β-(1,3)-Glucan Isolated from Genus Agrobacterium in Bone-Marrow Derived Macrophages and Mice Splenocytes vol.44, pp.05, 2016, https://doi.org/10.1142/S0192415X16500567
  26. Comparative chemical and biological investigations of β-glucan-containing products from shiitake mushrooms vol.18, 2015, https://doi.org/10.1016/j.jff.2015.08.022
  27. A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota vol.18, pp.9, 2017, https://doi.org/10.3390/ijms18091934
  28. (5-Hydroxy-4-oxo-4H-pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate, a kojic acid derivative, inhibits inflammatory mediator production via the suppression of Syk/Src and NF-κB activation vol.20, pp.1, 2014, https://doi.org/10.1016/j.intimp.2014.02.019
  29. In vitro immunostimulatory potential of fungal β-glucans in pacific red snapper ( Lutjanus peru ) cells vol.77, 2017, https://doi.org/10.1016/j.dci.2017.09.003
  30. vol.9, pp.1, 2018, https://doi.org/10.1039/C7FO01147D
  31. The scale-up cultivation of Candida utilis in waste potato juice water with glycerol affects biomass and β(1,3)/(1,6)-glucan characteristic and yield vol.102, pp.21, 2018, https://doi.org/10.1007/s00253-018-9357-y
  32. Consumption of β-glucans to spice up T cell treatment of tumors: a review vol.18, pp.10, 2018, https://doi.org/10.1080/14712598.2018.1523392
  33. Alkali treated antioxidative crude polysaccharide from Russula alatoreticula potentiates murine macrophages by tunning TLR/NF-κB pathway vol.9, pp.1, 2019, https://doi.org/10.1038/s41598-018-37998-2
  34. Trained Innate Immunity of Fish Is a Viable Approach in Larval Aquaculture vol.10, pp.1664-3224, 2019, https://doi.org/10.3389/fimmu.2019.00042
  35. Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite vol.2017, pp.None, 2012, https://doi.org/10.1155/2017/5061639
  36. 마이크로/나노-운반체를 이용한 톡소이드 항원의 효과적인 전달 방법 vol.28, pp.4, 2018, https://doi.org/10.5352/jls.2018.28.4.496
  37. 장수상황버섯 베타글루칸 추출물이 개미 집단생활에 미치는 영향 vol.16, pp.4, 2012, https://doi.org/10.14480/jm.2018.16.4.304
  38. Yeast-Derived β-Glucan in Cancer: Novel Uses of a Traditional Therapeutic vol.20, pp.15, 2019, https://doi.org/10.3390/ijms20153618
  39. Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer? vol.12, pp.1, 2012, https://doi.org/10.3390/cancers12010155
  40. Could the Induction of Trained Immunity by β-Glucan Serve as a Defense Against COVID-19? vol.11, pp.None, 2012, https://doi.org/10.3389/fimmu.2020.01782
  41. Immunomodulatory effects of β‐glucans derived from Euglena gracilis or Saccharomyces cerevisiae for hybrid striped bass (Morone chrysops × M. saxatilis) vol.51, pp.3, 2012, https://doi.org/10.1111/are.14472
  42. Antitumor, Anti-inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa : A Review of vol.12, pp.5, 2012, https://doi.org/10.3390/nu12051339
  43. Valorization of Deproteinated Potato Juice Water into β-Glucan Preparation of C. utilis Origin: Comparative Study of Preparations Obtained by Two Isolation Methods vol.11, pp.7, 2020, https://doi.org/10.1007/s12649-019-00641-w
  44. Training of Primary Chicken Monocytes Results in Enhanced Pro-Inflammatory Responses vol.7, pp.3, 2012, https://doi.org/10.3390/vetsci7030115
  45. Assessment of Polysaccharide and Biomass Production from Three White-Rot Fungi by Solid-State Fermentation Using Wood and Agro-Industrial Residues: A Kinetic Approach vol.11, pp.10, 2012, https://doi.org/10.3390/f11101055
  46. Yarrowia lipolytica N6-glucan protects goat leukocytes against Escherichia coli by enhancing phagocytosis and immune signaling pathway genes vol.150, pp.None, 2012, https://doi.org/10.1016/j.micpath.2021.104735
  47. Can medicinal mushrooms have prophylactic or therapeutic effect against COVID‐19 and its pneumonic superinfection and complicating inflammation? vol.93, pp.1, 2021, https://doi.org/10.1111/sji.12937
  48. Reviewing the Etiologic Agents, Microbe-Host Relationship, Immune Response, Diagnosis, and Treatment in Chromoblastomycosis vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/9742832
  49. Beta-D-glucan-based drug delivery system and its potential application in targeting tumor associated macrophages vol.253, pp.None, 2012, https://doi.org/10.1016/j.carbpol.2020.117258
  50. Microorganisms: A Potential Source of Bioactive Molecules for Antioxidant Applications vol.26, pp.4, 2012, https://doi.org/10.3390/molecules26041142
  51. Active Hexose-Correlated Compound Restores Gene Expression and Protein Secretion of Protective Cytokines of Immune Cells in a Murine Stress Model during Chlamydia muridarum Genital Infection vol.89, pp.5, 2012, https://doi.org/10.1128/iai.00786-20
  52. Fungal beta-glucans as adjuvants for treating cancer patients – A systematic review of clinical trials vol.40, pp.5, 2012, https://doi.org/10.1016/j.clnu.2020.11.029
  53. Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation vol.29, pp.3, 2012, https://doi.org/10.1007/s10787-021-00813-y
  54. Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma vol.22, pp.13, 2012, https://doi.org/10.3390/ijms22136833
  55. An appraisal of the metabolites, pharmacological and biotechnological significance of edible mushrooms vol.76, pp.3, 2012, https://doi.org/10.1080/0035919x.2021.1947921
  56. Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era vol.13, pp.11, 2021, https://doi.org/10.3390/nu13113960
  57. Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism vol.70, pp.12, 2012, https://doi.org/10.1007/s00262-021-02927-2
  58. Antioxidant Activity of Mushroom Extracts/Polysaccharides-Their Antiviral Properties and Plausible AntiCOVID-19 Properties vol.10, pp.12, 2012, https://doi.org/10.3390/antiox10121899
  59. Brewer's yeast polysaccharides — A review of their exquisite structural features and biomedical applications vol.277, pp.None, 2012, https://doi.org/10.1016/j.carbpol.2021.118826