DOI QR코드

DOI QR Code

Immunoenhancing Effects of Euglena gracilis on a Cyclophosphamide-Induced Immunosuppressive Mouse Model

  • Yang, Hyeonji (Department of Food Science and Technology, Seoul National University of Science and Technology) ;
  • Choi, Kwanyong (Department of Food Science and Technology, Seoul National University of Science and Technology) ;
  • Kim, Kyeong Jin (Department of Nano Bio Engineering, Seoul National University of Science and Technology) ;
  • Park, Soo-yeon (Lab of Nanobio, Seoul National University of Science and Technology) ;
  • Jeon, Jin-Young (BIO R&D center, Daesang Corp.) ;
  • Kim, Byung-Gon (BIO R&D center, Daesang Corp.) ;
  • Kim, Ji Yeon (Department of Food Science and Technology, Seoul National University of Science and Technology)
  • 투고 : 2021.12.20
  • 심사 : 2021.12.27
  • 발행 : 2022.02.28

초록

In this study, the effects of the immune stimulator Euglena gracilis (Euglena) in cyclophosphamide (CCP)-induced immunocompromised mice were assessed. The key component β-1,3-glucan (paramylon) constitutes 50% of E. gracilis. Mice were orally administered Euglena powder (250 and 500 mg/kg body weight (B.W.)) or β-glucan powder (250 mg/kg B.W.) for 19 days. In a preliminary immunology experiment, ICR mice were intraperitoneally injected with 80 mg of CCP/kg B.W. during the final 3 consecutive days. In the main experiment, BALB/c mice were treated with CCP for the final 5 days. To evaluate the enhancing effects of Euglena on the immune system, mouse B.W., the spleen index, natural killer (NK) cell activity and mRNA expression in splenocytes lungs and livers were determined. To detect cytokine and receptor expression, splenocytes were treated with 5 ㎍/ml concanavalin A or 1 ㎍/ml lipopolysaccharide. The B.W. and spleen index were significantly increased and NK cell activity was slightly enhanced in all the experimental groups compared to the CCP-only group. In splenocytes, the gene expression levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-10, IL-6, and IL-12 receptor were increased in the E. gracilis and β-glucan groups compared to the CCP-only group, but there was no significant difference. Treatment with 500 mg of Euglena/kg B.W. significantly upregulated dectin-1 mRNA expression in the lung and liver compared to the CCP-only group. These results suggest that Euglena may enhance the immune system by strengthening innate immunity through immunosuppression.

키워드

과제정보

This research was a part of a project titled 'Development of functional food material derived from marine resources, microalgae Euglena gracilis', funded by the Ministry of Oceans and Fisheries, Korea.

참고문헌

  1. Shin JS, Chung SH, Lee WS, Lee JY, Kim JL, Lee KT. 2018. Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice. Phytother. Res. 32: 132-139. https://doi.org/10.1002/ptr.5960
  2. Pearce EJ, Everts B. 2015. Dendritic cell metabolism. Nat. Rev. Immunol. 15: 18-29. https://doi.org/10.1038/nri3771
  3. Hile G, Kahlenberg JM, Gudjonsson JE. 2020. Recent genetic advances in innate immunity of psoriatic arthritis. Clin. Immunol. 214: 108405. https://doi.org/10.1016/j.clim.2020.108405
  4. Kurowska-Stolarska M, Alivernini S. 2017. Synovial tissue macrophages: friend or foe? RMD Open 3: e000527. https://doi.org/10.1136/rmdopen-2017-000527
  5. O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. 2006. T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat. Immunol. 7: 507-516. https://doi.org/10.1038/ni1332
  6. Ding J, Ning Y, Bai Y, Xu X, Sun X, Qi C. 2019. β-Glucan induces autophagy in dendritic cells and influences T-cell differentiation. Med. Microbiol. Immunol. 208: 39-48. https://doi.org/10.1007/s00430-018-0556-z
  7. Shokryazdan P, Faseleh Jahromi M, Navidshad B, Liang JB. 2017. Effects of prebiotics on immune system and cytokine expression. Med. Microbiol. Immunol. 206: 1-9. https://doi.org/10.1007/s00430-016-0481-y
  8. Phillips FC, Jensen GS, Showman L, Tonda R, Horst G, Levine R. 2019. Particulate and solubilized beta-glucan and non-beta-glucan fractions of Euglena gracilis induce pro-and anti-inflammatory innate immune cell responses and exhibit antioxidant properties. J. Inflamm. Res. 12: 49-64. https://doi.org/10.2147/JIR.S191824
  9. Buetow DE, Gilbert CW. 1982. Polypeptide composition of thylakoid membranes: two-dimensional gel analysis during development of Euglena chloroplasts. Prog. Clin. Biol. Res. 102 Pt B: 139-148.
  10. Nakashima A, Suzuki K, Asayama Y, Konno M, Saito K, Yamazaki N, et al. 2017. Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice. Biochem. Biophys. Res. Commun. 494: 379-383. https://doi.org/10.1016/j.bbrc.2017.09.167
  11. Nakashima A, Sugimoto R, Suzuki K, Shirakata Y, Hashiguchi T, Yoshida C, et al. 2019. Anti-fibrotic activity of Euglena gracilis and paramylon in a mouse model of non-alcoholic steatohepatitis. Food Sci. Nutr. 7: 139-147. https://doi.org/10.1002/fsn3.828
  12. Aemiro A, Watanabe S, Suzuki K, Hanada M, Umetsu K, Nishida T. 2016. Effects of Euglena (Euglena gracilis) supplemented to diet (forage: concentrate ratios of 60:40) on the basic ruminal fermentation and methane emissions in in vitro condition. Anim. Feed Sci. Technol. 212: 129-135. https://doi.org/10.1016/j.anifeedsci.2015.12.010
  13. Matsumoto T, Inui H, Miyatake K, Nakano Y, Murakami K. 2009. Comparison of Nutrients in Euglena with those in other representative food sources. Eco-Eng. 21: 81-86.
  14. Yasuda K, Nakashima A, Murata A, Suzuki K, Adachi T. 2020. Euglena Gracilis and beta-Glucan Paramylon Induce Ca(2+) signaling in intestinal tract epithelial, immune, and neural cells. Nutrients 12: 2293. https://doi.org/10.3390/nu12082293
  15. Russo R, Barsanti L, Evangelista V, Frassanito AM, Longo V, Pucci L, et al. 2017. Euglena gracilis paramylon activates human lymphocytes by upregulating pro-inflammatory factors. Food Sci. Nutr. 5: 205-214. https://doi.org/10.1002/fsn3.383
  16. Shimada R, Fujita M, Yuasa M, Sawamura H, Watanabe T, Nakashima A, et al. 2016. Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes. Food Funct. 7: 4655-4659. https://doi.org/10.1039/C6FO00606J
  17. Sakanoi Y, Shuang E, Yamamoto K, Ota T, Seki K, Imai M, et al. 2018. Simultaneous intake of Euglena Gracilis and vegetables synergistically exerts an anti-inflammatory effect and attenuates visceral fat accumulation by affecting gut microbiota in mice. Nutrients 10: 1417. https://doi.org/10.3390/nu10101417
  18. Okouchi R, E S, Yamamoto K, Ota T, Seki K, Imai M, et al. 2019. Simultaneous intake of Euglena gracilis and vegetables exerts synergistic anti-obesity and anti-inflammatory effects by modulating the gut microbiota in diet-induced obese mice. Nutrients. 11: 204. https://doi.org/10.3390/nu11010204
  19. Aoe S, Yamanaka C, Koketsu K, Nishioka M, Onaka N, Nishida N, et al. 2019. Effects of paramylon extracted from Euglena gracilis EOD-1 on parameters related to metabolic syndrome in diet-induced obese mice. Nutrients 11: 1674. https://doi.org/10.3390/nu11071674
  20. Ishibashi KI, Nishioka M, Onaka N, Takahashi M, Yamanaka D, Adachi Y, et al. 2019. Effects of Euglena gracilis EOD-1 ingestion on salivary IgA reactivity and health-related quality of life in humans. Nutrients 11: 1144. https://doi.org/10.3390/nu11051144
  21. Liu X, Zhang Z, Liu J, Wang Y, Zhou Q, Wang S, et al. 2019. Ginsenoside Rg3 improves cyclophosphamide-induced immunocompetence in Balb/c mice. Int. Immunopharmacol. 72: 98-111. https://doi.org/10.1016/j.intimp.2019.04.003
  22. Barnes H, Holland AE, Westall GP, Goh NS, Glaspole IN. 2018. Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst. Rev. 1: CD010908.
  23. Kim KJ, Paik HD, Kim JY. 2021. Immune-enhancing effects of Lactobacillus plantarum 200655 isolated from Korean kimchi in a cyclophosphamide-induced immunocompromised mouse model. J. Microbiol. Biotechnol. 31: 726-732. https://doi.org/10.4014/jmb.2103.03028
  24. Ahlmann M, Hempel G. 2016. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother. Pharmacol. 78: 661-671. https://doi.org/10.1007/s00280-016-3152-1
  25. Muller US, Wirth W, Junge-Hulsing G, Hauss WH. 1973. [Suppressive effects in mesenchyme and immunosuppressive effects of cytostatica]. Int. J. Clin. Pharmacol. 7: 228-233.
  26. Muller US, Wirth W, Thone F, Junge-Hulsing G, Hauss WH. 1973. [Animal experiments on the anti-inflammatory and immunosuppressive effect of cytostatic agents]. Arzneimittelforschung 23: 487-491.
  27. Li W, Hu X, Wang S, Jiao Z, Sun T, Liu T, et al. 2020. Characterization and anti-tumor bioactivity of astragalus polysaccharides by immunomodulation. Int. J. Biol. Macromol. 145: 985-997. https://doi.org/10.1016/j.ijbiomac.2019.09.189
  28. Mao GH, Ren Y, Li Q, Wu HY, Jin D, Zhao T, et al. 2016. Anti-tumor and immunomodulatory activity of selenium (Se)-polysaccharide from Se-enriched Grifola frondosa. Int. J. Biol. Macromol. 82: 607-613. https://doi.org/10.1016/j.ijbiomac.2015.10.083
  29. Han J, Xia J, Zhang L, Cai E, Zhao Y, Fei X, et al. 2019. Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide. J. Ginseng Res. 43: 618-624. https://doi.org/10.1016/j.jgr.2018.07.009
  30. Lei M, Wang J, Wang Y, Pang L, Wang Y, Xu W, et al. 2007. Study of the radio-protective effect of cuttlefish ink on hemopoietic injury. Asia Pac. J. Clin. Nutr. 16 Suppl 1: 239-243.
  31. Monmai C, You S, Park WJ. 2019. Immune-enhancing effects of anionic macromolecules extracted from Codium fragile on cyclophosphamide-treated mice. PLoS One 14: e0211570. https://doi.org/10.1371/journal.pone.0211570
  32. Lori A, Perrotta M, Lembo G, Carnevale D. 2017. The spleen: a hub connecting nervous and immune systems in cardiovascular and metabolic diseases. Int. J. Mol. Sci. 18: 1216. https://doi.org/10.3390/ijms18061216
  33. Sarangi I, Ghosh D, Bhutia SK, Mallick SK, Maiti TK. 2006. Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int. Immunopharmacol. 6: 1287-1297. https://doi.org/10.1016/j.intimp.2006.04.002
  34. Wahyuningsih SPA, Pramudya M, Putri IP, Winarni D, Savira NII, Darmanto W. 2018. Crude polysaccharides from okra pods (Abelmoschus esculentus) grown in Indonesia enhance the immune response due to bacterial infection. Adv. Pharmacol. Sci. 2018: 8505383.
  35. Zhang J, Zheng H, Diao Y. 2019. Natural killer cells and current applications of chimeric antigen receptor-modified NK-92 cells in tumor immunotherapy. Int. J. Mol. Sci. 20: 317. https://doi.org/10.3390/ijms20020317
  36. Campbell KS, Hasegawa J. 2013. Natural killer cell biology: an update and future directions. J. Allergy Clin. Immunol. 132: 536-544. https://doi.org/10.1016/j.jaci.2013.07.006
  37. Cerwenka A, Lanier LL. 2016. Natural killer cell memory in infection, inflammation and cancer. Nat. Rev. Immunol. 16: 112-123. https://doi.org/10.1038/nri.2015.9
  38. Hammer Q, Ruckert T, Romagnani C. 2018. Natural killer cell specificity for viral infections. Nat. Immunol. 19: 800-808. https://doi.org/10.1038/s41590-018-0163-6
  39. Pech MF, Fong LE, Villalta JE, Chan LJ, Kharbanda S, O'Brien JJ, et al. 2019. Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance. Elife 8: e47362. https://doi.org/10.7554/elife.47362
  40. Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. 1980. Role of NK cells in tumour growth and metastasis in beige mice. Nature 284: 622-624. https://doi.org/10.1038/284622a0
  41. Fehniger TA, Shah MH, Turner MJ, VanDeusen JB, Whitman SP, Cooper MA, et al. 1999. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J. Immunol. 162: 4511-4520.
  42. Ferlazzo G, Munz C. 2004. NK cell compartments and their activation by dendritic cells. J. Immunol. 172: 1333-1339. https://doi.org/10.4049/jimmunol.172.3.1333
  43. Zitvogel L, Terme M, Borg C, Trinchieri G. 2006. Dendritic cell-NK cell cross-talk: regulation and physiopathology. Curr. Top. Microbiol. Immunol. 298: 157-174.
  44. Chijioke O, Munz C. 2013. Dendritic cell derived cytokines in human natural killer cell differentiation and activation. Front. Immunol. 4: 365. https://doi.org/10.3389/fimmu.2013.00365
  45. Bald T, Pedde AM, Corvino D, Bottcher JP. 2020. The role of NK cell as central communicators in cancer immunity. Adv. Immunol. 147: 61-88. https://doi.org/10.1016/bs.ai.2020.06.002
  46. Paul S, Lal G. 2017. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front. Immunol. 8: 1124. https://doi.org/10.3389/fimmu.2017.01124
  47. Capellino S, Claus M, Watzl C. 2020. Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine. Cell. Mol. Immunol. 17: 705-711. https://doi.org/10.1038/s41423-020-0477-9
  48. Lee YJ, Paik DJ, Kwon DY, Yang HJ, Park Y. 2017. Agrobacterium sp.-derived beta-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study. Nutr. Res. Pract. 11: 43-50. https://doi.org/10.4162/nrp.2017.11.1.43
  49. Kumar BV, Connors TJ, Farber DL. 2018. Human T Cell development, localization, and function throughout life. Immunity 48: 202-213. https://doi.org/10.1016/j.immuni.2018.01.007
  50. Jansen JM, Gerlach T, Elbahesh H, Rimmelzwaan GF, Saletti G. 2019. Influenza virus-specific CD4+ and CD8+ T cell-mediated immunity induced by infection and vaccination. J. Clin. Virol. 119: 44-52. https://doi.org/10.1016/j.jcv.2019.08.009
  51. Fischer U, Yang JJ, Ikawa T, Hein D, Vicente-Duenas C, Borkhardt A, et al. 2020. Cell fate decisions: The role of transcription factors in early B-cell development and leukemia. Blood Cancer Discov. 1: 224-233. https://doi.org/10.1158/2643-3230.BCD-20-0011
  52. Kondo M. 2010. Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. Immunol. Rev. 238: 37-46. https://doi.org/10.1111/j.1600-065X.2010.00963.x
  53. Pelanda R, Torres RM. 2012. Central B-cell tolerance: where selection begins. Cold Spring Harb Perspect. Biol. 4: a007146. https://doi.org/10.1101/cshperspect.a007146
  54. Akrami M, Menzies R, Chamoto K, Miyajima M, Suzuki R, Sato H, et al. 2020. Circulation of gut-preactivated naive CD8(+) T cells enhances antitumor immunity in B cell-defective mice. Proc. Natl. Acad. Sci. USA 117: 23674-23683. https://doi.org/10.1073/pnas.2010981117
  55. Bastian D, Wu Y, Betts BC, Yu XZ. 2019. The IL-12 Cytokine and receptor family in graft-vs.-host disease. Front. Immunol. 10: 988. https://doi.org/10.3389/fimmu.2019.00988
  56. Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu CY, et al. 1996. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc. Natl. Acad. Sci. USA 93: 14002-14007. https://doi.org/10.1073/pnas.93.24.14002
  57. Wu C, Wang X, Gadina M, O'Shea JJ, Presky DH, Magram J. 2000. IL-12 receptor beta 2 (IL-12R beta 2)-deficient mice are defective in IL-12-mediated signaling despite the presence of high affinity IL-12 binding sites. J. Immunol. 165: 6221-6228. https://doi.org/10.4049/jimmunol.165.11.6221
  58. Chyuan IT, Lai JH. 2020. New insights into the IL-12 and IL-23: from a molecular basis to clinical application in immune-mediated inflammation and cancers. Biochem. Pharmacol. 175: 113928. https://doi.org/10.1016/j.bcp.2020.113928
  59. Vignali DA, Kuchroo VK. 2012. IL-12 family cytokines: immunological playmakers. Nat. Immunol. 13: 722-728. https://doi.org/10.1038/ni.2366
  60. Kak G, Raza M, Tiwari BK. 2018. Interferon-gamma (IFN-gamma): exploring its implications in infectious diseases. Biomol. Concepts 9: 64-79. https://doi.org/10.1515/bmc-2018-0007
  61. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. 2015. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74: 5-17. https://doi.org/10.1016/j.cyto.2014.09.011
  62. Park H-E, Lee W-K. 2018. Immune enhancing effects of Weissella cibaria JW15 on BALB/c mice immunosuppressed by cyclophosphamide. J. Funct. Foods 49: 518-525. https://doi.org/10.1016/j.jff.2018.09.003
  63. Guo Q, Bi D, Wu M, Yu B, Hu L, Liu C, et al. 2020. Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis. BMC Microbiol. 20: 171. https://doi.org/10.1186/s12866-020-01782-y
  64. Bedke T, Muscate F, Soukou S, Gagliani N, Huber S. 2019. Title: IL-10-producing T cells and their dual functions. Semin. Immunol. 44: 101335. https://doi.org/10.1016/j.smim.2019.101335
  65. Foulds KE, Rotte MJ, Seder RA. 2006. IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection. J. Immunol. 177: 2565-2574. https://doi.org/10.4049/jimmunol.177.4.2565
  66. Mumm JB, Emmerich J, Zhang X, Chan I, Wu L, Mauze S, et al. 2011. IL-10 elicits IFNgamma-dependent tumor immune surveillance. Cancer Cell 20: 781-796. https://doi.org/10.1016/j.ccr.2011.11.003
  67. Fujii S, Shimizu K, Shimizu T, Lotze MT. 2001. Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood 98: 2143-2151. https://doi.org/10.1182/blood.V98.7.2143
  68. Levy Y, Brouet JC. 1994. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J. Clin. Invest. 93: 424-428. https://doi.org/10.1172/JCI116977
  69. Xin G, Zander R, Schauder DM, Chen Y, Weinstein JS, Drobyski WR, et al. 2018. Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Nat. Commun. 9: 5037. https://doi.org/10.1038/s41467-018-07492-4
  70. Brown GD, Gordon S. 2001. A new receptor for β-glucans. Nature 413: 36-37. https://doi.org/10.1038/35092620
  71. Kalia N, Singh J, Kaur M. 2021. The role of dectin-1 in health and disease. Immunobiology 226: 152071. https://doi.org/10.1016/j.imbio.2021.152071
  72. Huysamen C, Brown GD. 2009. The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors. FEMS Microbiol. Lett. 290: 121-128. https://doi.org/10.1111/j.1574-6968.2008.01418.x
  73. Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S, et al. 2002. The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 169: 3876-3882. https://doi.org/10.4049/jimmunol.169.7.3876
  74. Willment JA, Marshall AS, Reid DM, Williams DL, Wong SY, Gordon S, et al. 2005. The human beta-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. Eur. J. Immunol. 35: 1539-1547. https://doi.org/10.1002/eji.200425725
  75. Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L, et al. 2002. Dectin-1 is a major beta-glucan receptor on macrophages. J. Exp. Med. 196: 407-412. https://doi.org/10.1084/jem.20020470
  76. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. 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
  77. Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, et al. 2005. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22: 507-517. https://doi.org/10.1016/j.immuni.2005.03.004
  78. De Marco Castro E, Calder PC, Roche HM. 2021. beta-1,3/1,6-Glucans and immunity: state of the art and future directions. Mol. Nutr. Food Res. 65: e1901071.
  79. Goodridge HS, Wolf AJ, Underhill DM. 2009. Beta-glucan recognition by the innate immune system. Immunol. Rev. 230: 38-50. https://doi.org/10.1111/j.1600-065X.2009.00793.x
  80. Inoue M, Okinaga T, Usui M, Kawano A, Thongsiri C, Nakashima K, et al. 2019. β-glucan suppresses cell death of ASC deficient macrophages invaded by periodontopathic bacteria through the caspase-11 pathway. FEMS Microbiol. Lett. 366: fnz093. https://doi.org/10.1093/femsle/fnz093
  81. Li X, Luo H, Ye Y, Chen X, Zou Y, Duan J, et al. 2019. betaglucan, a dectin1 ligand, promotes macrophage M1 polarization via NFkappaB/autophagy pathway. Int. J. Oncol. 54: 271-282.
  82. Brown GD, Gordon S. 2001. Immune recognition. A new receptor for beta-glucans. Nature 413: 36-37. https://doi.org/10.1038/35092620
  83. Herre J, Gordon S, Brown GD. 2004. Dectin-1 and its role in the recognition of beta-glucans by macrophages. Mol. Immunol. 40: 869-876. https://doi.org/10.1016/j.molimm.2003.10.007
  84. Calvayrac R, Laval-Martin D, Briand J, Farineau J. 1981. Paramylon synthesis by Euglena gracilis photoheterotrophically grown under low O2 pressure : Description of a mitochloroplast complex. Planta 153: 6-13. https://doi.org/10.1007/BF00385311
  85. Monfils AK, Triemer RE, Bellairs EF. 2011. Characterization of paramylon morphological diversity in photosynthetic euglenoids (Euglenales, Euglenophyta). Phycologia 50: 156-169. https://doi.org/10.2216/09-112.1
  86. Barsanti L, Gualtieri P. 2019. Paramylon, a potent immunomodulator from WZSL mutant of Euglena gracilis. Molecules 24: 3114. https://doi.org/10.3390/molecules24173114