Activation of macrophage mediated host defense against Salmonella typhimurium by Morus alba L.

  • BoYoon Chang
  • BongSeong Koo
  • HyeonCheol Lee
  • Joa Sub Oh
  • SungYeon Kim
Keywords: Morus alba L., TLR4, salmonella, immune defense, macrophage

Abstract

Background: The innate immune system plays a crucial role in the initiation and subsequent direction of
adaptive immune responses, as well as in the removal of pathogens that have been targeted by an adaptive
immune response.

Objective: Morus alba L. was reported to have immunostimulatory properties that might protect against infectious diseases. However, this possibility has not yet been explored. The present study investigated the protective and immune-enhancing ability of M. alba L. against infectious disease and the mechanisms involved.

Design: To investigate the immune-enhancing effects of M. alba L., we used a bacterial infection model.

Results and discussions: The lifespan of mice infected with a lethal dose of Salmonella typhimurium (1 × 107
colony forming units – CFU) was significantly extended when they were administered M. alba L. Furthermore,
M. alba L. activated macrophages, monocytes, and neutrophils and induced Th1 cytokines (IL-12,
IFN-γ, TNF-α) in mice infected with a sublethal dose (1 × 105 CFU) of S. typhimurium. M. alba L. significantly
stimulated the uptake of bacteria into peritoneal macrophages as indicated by increased phagocytosis.
Peritoneal macrophages derived from C3H/HeJ mice significantly inhibited M. alba L. induced NO production
and TNF-α secretion compared with peritoneal macrophages derived from C3H/HeN mice.

Conclusions: These results suggest that the innate immune activity of M. alba L. against bacterial infection in
mice occurs through activation of the TLR4 signaling pathway.

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References

  1. Qu Y, Li R, Jiang M, Wang X. Sucralose increases antimicrobial resistance and stimulates recovery of Escherichia coli mutants. Curr Microbiol 2017; 74(7): 885–8. doi: 10.1007/s00284-017-1255-5.

  2. Cherazard R, Epstein M, Doan TL, Salim T, Bharti S, Smith MA. Antimicrobial resistant Streptococcus pneumoniae: prevalence, mechanisms, and clinical implications. Am J Ther 2017; 24(3): e361–9. doi: 10.1097/mjt.0000000000000551.

  3. Shaker MA, Shaaban MI. Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic bacterial resistance: in vitro antibacterial study. Int J Pharm 2017; 525(1): 71–84. doi: 10.1016/j.ijpharm.2017.04.019.

  4. Luo A, Leach ST, Barres R, Hesson LB, Grimm MC, Simar D. The microbiota and epigenetic regulation of T helper 17/regulatory T cells: in search of a balanced immune system. Front Immunol 2017; 8: 417. doi: 10.3389/fimmu.2017.00417.

  5. McClure R, Massari P. TLR-dependent human mucosal epithelial cell responses to microbial pathogens. Front Immunol 2014; 5: 386. doi: 10.3389/fimmu.2014.00386.

  6. Gomes MT, Campos PC, de Almeida LA, Oliveira FS, Costa MM, Marim FM, et al. The role of innate immune signals in immunity to Brucella abortus. Front Cell Infect Microbiol 2012; 2: 130. doi: 10.3389/fcimb.2012.00130.

  7. Fieber C, Kovarik P. Responses of innate immune cells to group A Streptococcus. Front Cell Infect Microbiol 2014; 4: 140. doi: 10.3389/fcimb.2014.00140.

  8. Brito de Assis A, Dos Santos C, Dutra FP, de Oliveira Motta A, Costa FS, Navas CA, et al. Assessing antibacterial potential of components of Phyllomedusa distincta skin and its associated dermal microbiota. J Chem Ecol 2016; 42(2): 139–48. doi: 10.1007/s10886-016-0665-3.

  9. Zheng Z, Wei C, Guan K, Yuan Y, Zhang Y, Ma S, et al. Bacterial E3 Ubiquitin Ligase IpaH4.5 of Shigella flexneri targets TBK1 to Dampen the host antibacterial response. J Immunol 2016; 196(3): 1199–208. doi: 10.4049/jimmunol.1501045.

  10. Yang XY, Park GS, Lee MH, Chang IA, Kim YC, Kim SY, et al. Toll-like receptor 4-mediated immunoregulation by the aqueous extract of Mori Fructus. Phytother Res 2009; 23(12): 1713–20. doi: 10.1002/ptr.2818.

  11. Kim SB, Chang BY, Jo YH, Lee SH, Han SB, Hwang BY, et al. Macrophage activating activity of pyrrole alkaloids from Morus alba fruits. J Ethnopharmacol 2013; 145(1): 393–6. doi: 10.1016/j.jep.2012.11.007.

  12. Chang BY, Kim SB, Lee MK, Park H, Kim SY. Improved chemotherapeutic activity by Morus alba fruits through immune response of toll-like receptor 4. Int J Mol Sci. 2015; 16(10): 24139–58. doi: 10.3390/ijms161024139.

  13. Han EH, Choi JH, Hwang YP, Park HJ, Choi CY, Chung YC, et al. Immunostimulatory activity of aqueous extract isolated from Prunella vulgaris. Food Chem Toxicol 2009; 47(1): 62–9. doi: 10.1016/j.fct.2008.10.010.

  14. Wu J, Pugh R, Laughlin RC, Andrews-Polymenis H, McClelland M, Bäumler AJ, et al. High-throughput assay to phenotype Salmonella enterica typhimurium association, invasion, and replication in macrophages. J Vis Exp 2014; 11(90): e51759. doi: 10.3791/51759.

  15. Choi JW, Synytsya A, Capek P, Bleha R, Pohl R, Park YI. Structural analysis and anti-obesity effect of a pectic polysaccharide isolated from Korean mulberry fruit Oddi (Morus alba L.). Carbohydr Polym 2016; 146: 187–96. doi: 10.1016/j.carbpol.2016.03.043.

  16. Tirupathi RG, Suresh BK, Ujwal KJ, Sujana P, Raoa AV, Sreedhar AS. Anti-microbial principles of selected remedial plants from Southern India. Asian Pac J Trop Biomed 2011; 1(4): 298–305. doi: 10.1016/s2221-1691(11)60047-6.

  17. Kujawska M, Ewertowska M, Adamska T, Ignatowicz E, Flaczyk E, Przeor M, et al. Protective effect of Morus alba leaf extract on N-Nitrosodiethylamine-induced Hepatocarcinogenesis in rats. In vivo 2016; 30(6): 807–12.

  18. Yang Y, Zhang T, Xiao L, Yang L, Chen R. Two new chalcones from leaves of Morus alba L. Fitoterapia. 2010; 81(6): 614–16. doi: 10.1016/j.fitote.2010.03.005.

  19. Vick SJ, Bovet D, Anderson JR. How do African grey parrots (Psittacus erithacus) perform on a delay of gratification task? Anim Cogn 2010; 13(2): 351–8. doi: 10.1007/s10071-009-0284-2.

  20. Lee YJ, Choi DH, Kim EJ, Kim HY, Kwon TO, Kang DG, et al. Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet. Am J Chin Med 2011; 39(1): 39–52. doi: 10.1142/s0192415x11008634.

  21. Jung JW, Ko WM, Park JH, Seo KH, Oh EJ, Lee DY, et al. Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotective activities. Arch Pharm Res 2015; 38(11): 2066–75. doi: 10.1007/s12272-015-0613-8.

  22. Seo KH, Lee DY, Jeong RH, Lee DS, Kim YE, Hong EK, et al. Neuroprotective effect of prenylated arylbenzofuran and flavonoids from morus alba fruits on glutamate-induced oxidative injury in HT22 hippocampal cells. J Med Food 2015; 18(4): 403–8. doi: 10.1089/jmf.2014.3196.

  23. Jiao Y, Wang X, Jiang X, Kong F, Wang S, Yan C. Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and streptozotocin-induced type 2 diabetes in rats. J Ethnopharmacol 2017; 199: 119–27. doi: 10.1016/j.jep.2017.

  24. Ye M, Ke Y, Liu B, Yuan Y, Wang F, Bu S, et al. Root bark of Morus alba ameliorates the depressive-like behaviors in diabetic rats. Neurosci Lett 2017; 637: 136–41. doi: 10.1016/j.neulet.2016.11.036.

  25. Chang BY, Kim SB, Lee MK, Park H, Kim SY. Nonclinical safety assessment of Morus alba L. fruits: study of 90-D toxicity in Sprague Dawley Rats and genotoxicity in Salmonella. J Food Sci 2016; 81(5): T1328–35. doi: 10.1111/1750-3841.13285.

  26. Kim SB, Chang BY, Hwang BY, Kim SY, Lee MK. Pyrrole alkaloids from the fruits of Morus alba. Bioorg Med Chem Lett 2014; 24(24): 5656–9. doi: 10.1016/j.bmcl.2014.10.073.

  27. Hurley D, McCusker MP, Fanning S, Martins M. Salmonella-host interactions – modulation of the host innate immune system. Front Immunol 2014; 5: 481. doi: 10.3389/fimmu.2014.00481.

  28. Zhou D, Yang K, Chen L, Zhang W, Xu Z, Zuo J, et al. Promising landscape for regulating macrophage polarization: epigenetic viewpoint. Oncotarget. 2017; 8(34): 57693–706. doi: 10.18632/oncotarget.17027.

  29. Chu HB, Zhang TG, Zhao JH, Jian FG, Xu YB, Wang T, Wang M, Tang JY, Sun HJ, Li K, Guo WJ, Zhu XJ. Assessment of immune cells and function of the residual spleen after subtotal splenectomy due to splenomegaly in cirrhotic patients. BMC immunology 2014; 15: 42. doi: 10.1186/s12865-014-0042-3

  30. Kalupahana RS, Mastroeni P, Maskell D, Blacklaws BA. Activation of murine dendritic cells and macrophages induced by Salmonella enterica serovar Typhimurium. Immunology 2005; 115(4): 462–72. doi: 10.1111/j.1365-2567.2005.02180.x.

  31. Perkins DJ, Rajaiah R, Tennant SM, Ramachandran G, Higginson EE, Dyson TN, et al. Salmonella typhimurium co-opts the host type I IFN system to restrict macrophage innate immune transcriptional responses selectively. J Immunol. 2015; 195(5): 2461–71. doi: 10.4049/jimmunol.1500105.

  32. Fernandez-Cabezudo MJ, Mechkarska M, Azimullah S, al-Ramadi BK. Modulation of macrophage proinflammatory functions by cytokine-expressing Salmonella vectors. Clin Immunol 2009; 130(1): 51–60. doi: 10.1016/j.clim.2008.08.017.

  33. Hamidzadeh K, Mosser DM. Purinergic signaling to terminate TLR responses in macrophages. Front Immunol 2016; 7: 74. doi: 10.3389/fimmu.2016.00074.

Published
2018-02-21
How to Cite
Chang B., Koo B., Lee H., Oh J. S., & Kim S. (2018). Activation of macrophage mediated host defense against <em>Salmonella typhimurium by Morus alba</em&gt; L. Food & Nutrition Research, 62. https://doi.org/10.29219/fnr.v62.1289
Section
Original Articles