Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Micronized and Heat-Treated Lactobacillus plantarum LM1004 Stimulates Host Immune Responses Via the TLR-2/MAPK/NF-κB Signalling Pathway In Vitro and In Vivo

  • Lee, Jisun (Department of Biotechnology, The Catholic University of Korea) ;
  • Jung, Ilseon (LACTOMASON) ;
  • Choi, Ji Won (Department of Biotechnology, The Catholic University of Korea) ;
  • Lee, Chang Won (Department of Biotechnology, The Catholic University of Korea) ;
  • Cho, Sarang (Department of Biotechnology, The Catholic University of Korea) ;
  • Choi, Tae Gyu (Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University) ;
  • Sohn, Minn (LACTOMASON) ;
  • Park, Yong Il (Department of Biotechnology, The Catholic University of Korea)
  • Received : 2018.12.27
  • Accepted : 2019.04.09
  • Published : 2019.05.28
Download PDF
⟨ Previous Next ⟩

Abstract

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

Keywords

References

  1. Hwang JH, Lim SB. 2017. Immunostimulatory activity of Opuntia ficus-indica var. Saboten cladodes fermented by Lactobacillus plantarum and Bacillus subtilis in RAW 264.7 macrophages. J. Med. Food 20: 131-139. https://doi.org/10.1089/jmf.2016.3831
  2. Adams CA. 2010. The probiotic paradox: live and dead cells are biological response modifiers. Nutr. Res. Rev. 23: 37-46. https://doi.org/10.1017/S0954422410000090
  3. Aoki-Yoshida A, Saito S, Tsuruta T, Ohsumi A, Tsunoda H, Sonoyama K. 2017. Exosomes isolated from sera of mice fed Lactobacillus strains affect inflammatory cytokine production in macrophages in vitro. Biochem. Biophys. Res. Commun. 489:248-254. https://doi.org/10.1016/j.bbrc.2017.05.152
  4. Chuang L, Wu KG, Pai C, Hsieh PS, Tsai JJ, Yen JH, et al. 2007. Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells. J. Agr. Food Chem. 55: 11080-11086. https://doi.org/10.1021/jf071786o
  5. He F, Morita H, Kubota A, Ouwehand AC, Hosoda M, Hiramatsu M, et al. 2005. Effect of orally administered nonviable Lactobacillus cells on murine humoral immune responses. Microbiol. Immunol. 49: 995-999.
  6. Ou CC, Lin SL, Tsai JJ, Lin MY. 2011. Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing the immune response toward Th1 polarization. J. Food Sci. 76: M260-267. https://doi.org/10.1111/j.1750-3841.2011.02161.x
  7. de Almada CN, Almada CN, Martinez RCR, Sant'Ana AS. 2016. Paraprobiotics: Evidences on their ability to modify biological responses, inactivation methods and perspectives on their application in foods. Trends Food Sci. Technol. 58:96-114. https://doi.org/10.1016/j.tifs.2016.09.011
  8. Sasaki E, Suzuki S, Fukui Y, Yajima N. 2015. Cell-bound exopolysaccharides of Lactobacillus brevis KB290 enhance cytotoxic activity of mouse splenocytes. J. Appl. Microbiol. 118: 506-514. https://doi.org/10.1111/jam.12686
  9. Lee HA, Kim H, Lee KW, Park KY. 2015. Dead nano-sized Lactobacillus plantarum inhibits azoxymethane/dextran sulfate sodium-induced colon cancer in Balb/c mice. J. Med. Food. 18: 1400-1405. https://doi.org/10.1089/jmf.2015.3577
  10. T. Kan, M. Ohwaki, Lactobacillus having ability to induce IL-12 production, and method for culturing same, US Patents (2013)
  11. Tabata Y, Inoue Y, Ikada Y. 1996. Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. Vaccine 14: 1677-1685. https://doi.org/10.1016/S0264-410X(96)00149-1
  12. Lee HA, Kim H, Lee KW, Park KY. 2016. Dead Lactobacillus plantarum stimulates and skews immune responses toward T helper 1 and 17 polarizations in RAW 264.7 cells and mouse splenocytes. J. Microbiol. Biotechnol. 26: 469-476. https://doi.org/10.4014/jmb.1511.11001
  13. Jung I, Lovitt RW. 2010. A comparative study of the growth of lactic acid bacteria in a pilot scale membrane bioreactor. J. Chem. Technol. Biotechnol. 85: 1250-1259. https://doi.org/10.1002/jctb.2424
  14. Jung IS, Oh MK, Cho YC, Kong IS. 2011. The viability to a wall shear stress and propagation of Bifidobacterium longum in the intensive membrane bioreactor. Appl. Microbiol. Biotechnol. 92: 939-949. https://doi.org/10.1007/s00253-011-3387-z
  15. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  16. Lee J, Choi JW, Sohng JK, Pandey RP, Park YI. 2016. The immunostimulating activity of quercetin 3-O-xyloside in murine macrophages via activation of the ASK1/MAPK/ NF-kappaB signaling pathway. Int. Immunopharmacol. 31: 88-97. https://doi.org/10.1016/j.intimp.2015.12.008
  17. Chien AC, Hill NS, Levin PA. 2012. Cell size control in bacteria. Curr. Biol. 22: R340-349. https://doi.org/10.1016/j.cub.2012.02.032
  18. Vassalli P. 1992. The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 10: 411-452. https://doi.org/10.1146/annurev.iy.10.040192.002211
  19. Bogdan C. 2001. Nitric oxide and the immune response. Nat. Immunol. 2: 907-916. https://doi.org/10.1038/ni1001-907
  20. Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ. 2000. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J. Immunol. 165: 618-622. https://doi.org/10.4049/jimmunol.165.2.618
  21. Takeuchi O, Akira S. 2001. Toll-like receptors; their physiological role and signal transduction system. Int. Immunopharmacol. 1: 625-635. https://doi.org/10.1016/S1567-5769(01)00010-8
  22. Xie QW, Kashiwabara Y, Nathan C. 1994. Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J. Biol. Chem. 269: 4705-4708. https://doi.org/10.1016/S0021-9258(17)37600-7
  23. Gill HS, Rutherfurd KJ, Prasad J, Gopal PK. 2000. Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019). Br. J. Nutr. 83: 167-176. https://doi.org/10.1017/S0007114500000210
  24. Galdeano CM, de Moreno de LeBlanc A, Vinderola G, Bonet ME, Perdigon G. 2007. Proposed model: mechanisms of immunomodulation induced by probiotic bacteria. Clin. Vaccine Immunol. 14: 485-492. https://doi.org/10.1128/CVI.00406-06
  25. Dogi CA, Galdeano CM, Perdigon G. 2008. Gut immune stimulation by non pathogenic Gram(+) and Gram(-) bacteria. Comparison with a probiotic strain. Cytokine 41: 223-231. https://doi.org/10.1016/j.cyto.2007.11.014
  26. Iwasaki A, Medzhitov R. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995. https://doi.org/10.1038/ni1112
  27. van Bergenhenegouwen J, Kraneveld AD, Rutten L, Kettelarij N, Garssen J, Vos AP. 2014. Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis. PLoS One 9: e89121. https://doi.org/10.1371/journal.pone.0089121
  28. Zeuthen LH, Fink LN, Frokiaer H. 2008. Toll-like receptor 2 and nucleotide-binding oligomerization domain-2 play divergent roles in the recognition of gut-derived lactobacilli and bifidobacteria in dendritic cells. Immunology 124: 489-502. https://doi.org/10.1111/j.1365-2567.2007.02800.x
  29. Plantinga TS, van Maren WW, van Bergenhenegouwen J, Hameetman M, Nierkens S, Jacobs C, et al. 2011. Differential Toll-like receptor recognition and induction of cytokine profile by Bifidobacterium breve and Lactobacillus strains of probiotics. Clin. Vaccine Immunol. 18: 621-628. https://doi.org/10.1128/CVI.00498-10
  30. Senthil Kumar KJ, Wang SY. 2009. Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-kappaB and MAPKs signaling pathways. Planta Med. 75: 494-500. https://doi.org/10.1055/s-0029-1185309

Cited by

  1. Impact of Heat-Killed Lactobacillus casei Strain IMAU60214 on the Immune Function of Macrophages in Malnourished Children vol.12, pp.8, 2020, https://doi.org/10.3390/nu12082303
  2. Synthesized swine influenza NS1 antigen provides a protective immunity in a mice model vol.23, 2019, https://doi.org/10.4142/jvs.19411
  3. Effects of oral administration of Spirulina platensis and probiotics on serum immunity indexes, colonic immune factors, fecal odor, and fecal flora in mice vol.92, pp.1, 2021, https://doi.org/10.1111/asj.13593
  4. The Panda-Derived Lactobacillus plantarum G201683 Alleviates the Inflammatory Response in DSS-Induced Panda Microbiota-Associated Mice vol.12, 2019, https://doi.org/10.3389/fimmu.2021.747045