Effects of probiotics on the enhancement of the innate mucosal immune response against pathogenic bacteria
Background and Objectives: Probiotics have been widely used for host immune system enhancement but with limited knowledge regarding the immunomodulation mechanisms by which they assist the mucosal innate immune response. We investigated the effects of probiotics on the modulation of the innate mucosal immune response particularly in association with Toll-like receptor (TLR)-2, TLR-4 and nuclear factor-kappa B (NF-κB) p65 and p105.
Materials and Methods: We randomized 24 male BALB/c mice into four groups. Two groups were administered probiotics for 21 consecutive days; one of these groups was challenged with Lipopolysaccharide (LPS) on day 15. The third group was challenged with only LPS. The fourth group remained untreated. All mice were sacrificed after 21 days. An immunohistochemistry procedure on the ileum was performed and monoclonal antibodies specific for TLR-2, TLR-4 and NF-κB p65 and p105 were used for the analysis of innate lymphoid cells.
Results: In the LPS-only treated group, there was a significant decrease in p105, indicating an alternative transcription pathway for the process of pro-inflammatory cytokine production. In the probiotics-only treated group there was significant enhancement of TLR-2 and TLR-4 and NF-κB p65 and p105. When mice treated with probiotics were exposed to LPS, there was a significant decrease in NF-κB p65 and p105, indicating employment of the classical pathway for pro-inflammatory cytokine production.
Conclusion: Probiotics can enhance the innate mucosal immune response in healthy mice and can maintain the homeostasis of the gut mucosal immune response against LPS through the activation of the classical NF-κB pathway.
2. Siegmund B, Zeitz M. Innate and adaptive immunity in inflammatory bowel disease. World J Gastroenterol 2011; 17: 3178-3183.
3. MacDonald TT, Gordon JN. Bacterial regulation of intestinal immune responses. Gastroenterol Clin North Am 2005; 34: 401-412.
4. Gogineni VK, Morrow LE, Malesker MA. Probiotics: Mechanisms of Action and Clinical Applications. J Prob Health 2013; 1: 1.
5. Huang Y, Shao XM, Neu J. Immunonutrients and neonates. Eur J Pediatr 2003; 162: 122-128.
6. Novak N, Leung DYM. Diet and allergy: You are what you eat? J Allergy Clin Immunol 2005; 115: 1235-1237.
7. Urdaci MC, Bressollier P, Pinchuk I. Bacillus clausii probiotic strains. J Clin Gastroenterol 2004; 38(6 Suppl):S86-90.
8. Galdeano CM, De Leblanc AD, Vinderola G, Bonet MB, Perdigon G. Proposed model: Mechanisms of immunomodulation induced by probiotic bacteria. Clin Vaccine Immunol 2007; 14: 485-492.
9. Floch MH, Walker WA, Guandalini S, Hibberd P, Gorbach S, Surawicz C, et al. Recommendations for Probiotic Use−2008. J Clin Gastroenterol 2008; 42 Suppl 2:S104-108.
10. Berman SH, Eichelsdoerfer P, Yim D, Elmer GW, Wenner CA. Daily ingestion of a nutritional probiotic supplement enhances innate immune function in healthy adults. Nutr Res 2006; 26: 454-459.
11. Nova E, Viadel B, Blasco M, Marcos A. Effects of synbiotics on intestinal and immune function. Proc Nutr Soc 2008; 67: E4.
12. Sansonetti PJ. The innate signaling of dangers and the dangers of innate signaling. Nat Immunol 2006; 7: 1237-1242.
13. Creagh EM, O’Neill LAJ. TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol 2006; 27: 352-357.
14. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 2007; 19: 3-10.
15. Isolauri E, Salminen S. Probiotics, gut inflammation and barrier function.Gastroenterol Clin North Am 2005; 34: 437-450.
16. Dogi CA, Galdeano CM, Perdigón G. Gut immune stimulation by non pathogenic Gram(+) and Gram(-) bacteria. Comparison with a probiotic strain. Cytokine 2008; 41: 223-231.
17. Perdigon G, Vintini E, Alvarez S, Medina M, Medici M. Study of the possible mechanism involved in the mucosal immune system activation by lactic acid bacteria. J Dairy Sci 1999; 82:1108-1114.
18. Fang H, Elina T, Heikki A, Seppo S. Modulation of humoral immune response through probiotic intake. FEMS Immunol Med Microbiol 2000; 29: 47-52.
19. Galdeano CM, Perdigo G. The Probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clin Vaccine Immunol 2006; 13: 219-226.
20. Cross ML, Ganner A, Teilab D, Fray LM. Patterns of cytokine induction by gram-positive and gram-negative probiotic bacteria. FEMS Immunol Med Microbiol 2004; 42: 173-180.
21. Blum S, Schiffrin E. Intestinal microflora and homeostasis of the mucosal immune response: implications for probiotic bacteria? Curr Issues Intest Microbiol 2003; 4: 53-60.
22. Rakoff-Nahoum S, Medzhitov R. Innate immune recognition of the indigenous microbial flora. Mucosal Immunol 2008; 1 Suppl 1:S10-14.
23. Kim SO, Sheikh HI, Ha SD, Martins A, Reid G. G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell Microbiol 2006; 8: 1958-1971.
24. Staege H, Schaffner A, Schneemann M. Human toll-like receptors 2 and 4 are targets for deactivation of mononuclear phagocytes by interleukin-4. Immunol Lett 2000; 71: 1-3.
25. von der Weid T, Bulliard C, Schiffrin EJ. Induction by a lactic acid bacterium of a population of CD4+ T cells with low proliferative capacity that produce transforming growth factor and interleukin-10. Clin Diagn Lab Immunol 2001; 8: 695-701.
26. Mestas J, Hughes CCW. Of mice and not men: differences between mouse and human immunology. J Immunol 2004; 172: 2731-2738.
27. Kim YG, Ohta T, Takahashi T, Kushiro A, Nomoto K, Yokokura T, et al. Probiotic Lactobacillus casei activates innate immunity via NF-κB and p38 MAP kinase signaling pathways. Microb Infect 2006; 8: 994-1005.
28. Ghosh S, Hayden MS. New regulators of NF-κB in inflammation. Nat Rev Immunol 2008; 8: 837-848.
29. Hong M, Kim SW, Han SH, Kim DJ, Suk KT, Kim YS. Probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052) reduce the expression of Toll-like receptor 4 in mice with alcoholic liver disease. PLoS One 2015; 10(2): e0117451.
30. Karlsson M, Scherbak N, Reid G, Jass J. Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4. BMC Microbiol 2012; 12: 15.
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