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Mechanisms involved in the immunostimulation by probiotic fermented milk

Published online by Cambridge University Press:  29 July 2009

Carolina Maldonado Galdeano ,
Alejandra de Moreno de LeBlanc ,
Esteban Carmuega ,
Ricardo Weill  and
Gabriela Perdigón
Carolina Maldonado Galdeano
Affiliation:
Centro de Referencia para Lactobacilos (CERELA-CONICET), Chacabuco 145, San Miguel de Tucumán (T4000ILC) Tucumán, Argentina Cátedra de Inmunología, Instituto de Microbiología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Argentina
Alejandra de Moreno de LeBlanc
Affiliation:
Centro de Referencia para Lactobacilos (CERELA-CONICET), Chacabuco 145, San Miguel de Tucumán (T4000ILC) Tucumán, Argentina
Esteban Carmuega
Affiliation:
Nutritia, Buenos Aires, Argentina
Ricardo Weill
Affiliation:
Departamento de investigación y Desarrollo, DANONE Argentina S.A.Buenos Aires, Argentina
Gabriela Perdigón*
Affiliation:
Centro de Referencia para Lactobacilos (CERELA-CONICET), Chacabuco 145, San Miguel de Tucumán (T4000ILC) Tucumán, Argentina Cátedra de Inmunología, Instituto de Microbiología, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Argentina
*
*For correspondence; e-mail: perdigon@cerela.org.ar
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Abstract

The intestinal ecosystem contains a normal microbiota, non-immune cells and immune cells associated with the intestinal mucosa. The mechanisms involved in the modulation of the gut immune system by probiotics are not yet completely understood. The present work studies the effect of a fermented milk containing probiotic bacterium Lactobacillus (Lb.) casei DN114001 on different parameters of the gut immune system involved with the nonspecific, innate and adaptive response. BALB/c mice received the probiotic bacterium Lb. casei DN114001 or the probiotic fermented milk (PFM). The interaction of the probiotic bacteria with the intestine was studied by electron and fluorescence microscopy. The immunological parameters were studied in the intestinal tissue and in the supernatant of intestinal cells (IC). Results showed that the probiotic bacterium interact with the IC. The whole bacterium or its fragments make contact with the gut associated immune cells. The PFM stimulated the IC with IL-6 release, as well as cells related to the nonspecific barrier and with the immune cells associated with the gut. This last activity was observed through the increase in the population of different immune cells: T lymphocytes and IgA+ B lymphocytes, and by the expression of cell markers related to both innate and adaptive response (macrophages). PFM was also able to activate the enzyme calcineurine responsible for the activation of the transcriptional factor NFAT. PFM induced mucosal immune stimulation reinforcing the non-specific barrier and modulating the innate immune response in the gut, maintaining the intestinal homeostasis.

Keywords

fermented milkimmunostimulationprobiotic bacterium
Type
Research Article
Information
Journal of Dairy Research , Volume 76 , Issue 4 , November 2009 , pp. 446 - 454
Copyright
Copyright © Proprietors of Journal of Dairy Research 2009

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References

Allavena, P, Chieppa, M, Monti, P & Piemonti, L 2004 From pattern recognition receptor to regulator of homeostasis: the double-faced macrophage mannose receptor. Critical Reviews in Immunology 24(3) 179–192CrossRefGoogle ScholarPubMed
Beagley, KW, Eldridge, JH, Aicher, WK, Mestecky, J, Di Fabio, S, Kiyono, H & McGhee, JR 1991 Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6. Cytokine 3(2) 107–116CrossRefGoogle ScholarPubMed
Bezkorovainy, A 2001 Probiotics: determinants of survival and growth in the gut. American Journal of Clinical Nutrition 73(2 Suppl) 399S–405SCrossRefGoogle ScholarPubMed
Conboy, IM, Manoli, D, Mhaiskar, V & Jones, PP 1999 Calcineurin and vacuolar-type H+-ATPase modulate macrophage effector functions. Proceedings of the National Academy of Sciences of the United States of America 96(11) 6324–6329CrossRefGoogle ScholarPubMed
Cox, KH, Ofek, I & Hasty, DL 2007 Enhancement of macrophage stimulation by lipoteichoic acid and the costimulant hemoglobin is dependent on Toll-like receptors 2 and 4. Infection and Immunity 75(5) 2638–2641CrossRefGoogle ScholarPubMed
Crabtree, GR 2001 Calcium, calcineurin, and the control of transcription. The Journal of Biological Chemistry 276(4) 2313–2316CrossRefGoogle ScholarPubMed
de Moreno de Leblanc, A, Chaves, S, Carmuega, E, Weill, R, Antoine, J & Perdigon, G 2008a Effect of long-term continuous consumption of fermented milk containing probiotic bacteria on mucosal immunity and the activity of peritoneal macrophages. Immunobiology 213(2) 97–108CrossRefGoogle ScholarPubMed
de Moreno de LeBlanc, A, Dogi, CA, Maldonado Galdeano, C, Carmuega, E, Weill, R & Perdigón, G 2008b Effect of the administration of fermented milk containing Lactobacillus casei DN-114001 on intestinal microflora and immune cells associated to the gut of neonate mice. BMC Immunology 9(27)CrossRefGoogle Scholar
de Moreno de LeBlanc, A, Maldonado Galdeano, C, Chaves, S & Perdigón, G 2005a Oral administration of Lactobacillus casei CRL 431 increases immunity in bronchus and mammary glands. European Journal of Inflammation, 23–28CrossRefGoogle Scholar
de Moreno de LeBlanc, A, Matar, C, LeBlanc, N & Perdigon, G 2005b Effects of milk fermented by Lactobacillus helveticus R389 on a murine breast cancer model. Breast Cancer Research 7(4) R477–489CrossRefGoogle ScholarPubMed
Dogi, CA, Galdeano, CM & Perdigon, G 2008 Gut immune stimulation by non pathogenic Gram(+) and Gram(-) bacteria. Comparison with a probiotic strain. Cytokine 41(3) 223–231Google ScholarPubMed
Eutamene, H, Lamine, F, Chabo, C, Theodorou, V, Rochat, F, Bergonzelli, GE, Corthesy-Theulaz, I, Fioramonti, J & Bueno, L 2007 Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats. Journal of Nutrition 137(8) 1901–1907CrossRefGoogle ScholarPubMed
Galdeano, CM, de Moreno de LeBlanc, A, Vinderola, G, Bonet, ME & Perdigon, G 2007 Proposed model: mechanisms of immunomodulation induced by probiotic bacteria. Clinical and Vaccine Immunology 14(5) 485–492CrossRefGoogle ScholarPubMed
Galdeano, CM & Perdigon, G 2004 Role of viability of probiotic strains in their persistence in the gut and in mucosal immune stimulation. Journal of Applied Microbiology 97(4) 673–681CrossRefGoogle ScholarPubMed
Galdeano, CM & Perdigon, G 2006 The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clinical and Vaccine Immunology 13(2) 219–226CrossRefGoogle ScholarPubMed
Gaskins, HR 1998 Immunological development and mucosal defense in the pig intestine. In Chadwick eds. Progress in Pig Science, pp. 81–100. (Eds Wiseman, J & Varley, MA). Nottingham, UK: Nottingham University PressGoogle Scholar
Haller, D, Bode, C, Hammes, WP, Pfeifer, AM, Schiffrin, EJ & Blum, S 2000 Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut 47(1) 79–87CrossRefGoogle ScholarPubMed
Isono, A, Katsuno, T, Sato, T, Nakagawa, T, Kato, Y, Sato, N, Seo, G, Suzuki, Y & Saito, Y 2007 Clostridium butyricum TO-A culture supernatant downregulates TLR4 in human colonic epithelial cells. Digestive Diseases and Sciences 52(11) 2963–2971CrossRefGoogle ScholarPubMed
Jang, MH, Kweon, MN, Iwatani, K, Yamamoto, M, Terahara, K, Sasakawa, C, Suzuki, T, Nochi, T, Yokota, Y, Rennert, PD, Hiroi, T, Tamagawa, H, Iijima, H, Kunisawa, J, Yuki, Y & Kiyono, H 2004 Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proceedings of the National Academy of Sciences of the United States of America 101(16) 6110–6115CrossRefGoogle ScholarPubMed
Kaminuma, O, Kitamura, F, Kitamura, N, Hiroi, T, Miyoshi, H, Miyawaki, A & Miyatake, S 2008 Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T cells. Journal of Immunology 180(1) 319–326CrossRefGoogle ScholarPubMed
Lamm, ME 1998 Current concepts in mucosal immunity. IV. How epithelial transport of IgA antibodies relates to host defense. American Journal of Physiology 274(4 Pt 1) G614–617Google ScholarPubMed
Lin, HH, Faunce, DE, Stacey, M, Terajewicz, A, Nakamura, T, Zhang-Hoover, J, Kerley, M, Mucenski, ML, Gordon, S & Stein-Streilein, J 2005 The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. Journal of Experimental Medicine 201(10) 1615–1625CrossRefGoogle ScholarPubMed
Mack, DR, Michail, S, Wei, S, McDougall, L & Hollingsworth, MA 1999 Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. American Journal of Physiology 276(4 Pt 1) G941–950Google ScholarPubMed
Medici, M, Vinderola, CG, Weill, R & Perdigon, G 2005 Effect of fermented milk containing probiotic bacteria in the prevention of an enteroinvasive Escherichia coli infection in mice. Journal of Dairy Research 72(2) 243–249CrossRefGoogle ScholarPubMed
Olson, EN & Williams, RS 2000 Remodeling muscles with calcineurin. Bioessays 22(6) 510–5193.0.CO;2-1>CrossRefGoogle ScholarPubMed
Rescigno, M, Urbano, M, Valzasina, B, Francolini, M, Rotta, G, Bonasio, R, Granucci, F, Kraehenbuhl, JP & Ricciardi-Castagnoli, P 2001 Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature in Immunology 2(4) 361–367CrossRefGoogle ScholarPubMed
Rusnak, F & Mertz, P 2000 Calcineurin: form and function. Physiological Reviews 80(4) 1483–1521CrossRefGoogle ScholarPubMed
Tappenden, KA & Deutsch, AS 2007 The physiological relevance of the intestinal microbiota–contributions to human health. Journal of the American College of Nutrition 26(6) 679S–683SCrossRefGoogle ScholarPubMed
Tsuboi, A, Masuda, ES, Naito, Y, Tokumitsu, H, Arai, K & Arai, N 1994 Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells: involvement of the conserved lymphokine element 0. Molecular Biology of the Cell 5(1), 119–128CrossRefGoogle Scholar
Verdu, EF, Bercik, P, Verma-Gandhu, M, Huang, XX, Blennerhassett, P, Jackson, W, Mao, Y, Wang, L, Rochat, F & Collins, SM 2006 Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 55(2) 182–190CrossRefGoogle ScholarPubMed
Vinderola, G, Matar, C & Perdigon, G 2005 Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvement of toll-like receptors. Clinical and Diagnostic Laboratory Immunology 12(9) 1075–1084Google ScholarPubMed
Wen, H, Schaller, MA, Dou, Y, Hogaboam, CM & Kunkel, SL 2007 Dendritic cells at the interface of innate and acquired immunity: the role for epigenetic changes. Journal of Leukocyte Biology 83(3) 439–446CrossRefGoogle ScholarPubMed
Wijburg, OL, Heemskerk, MH, Boog, CJ & Van Rooijen, N 1997 Role of spleen macrophages in innate and acquired immune responses against mouse hepatitis virus strain A59. Immunology 92(2) 252–258CrossRefGoogle ScholarPubMed
Zuccotti, GV, Meneghin, F, Raimondi, C, Dilillo, D, Agostoni, C, Riva, E & Giovannini, M 2008 Probiotics in clinical practice: an overview. The Journal of International Medicine Research 36 (Suppl 1) 1A–53ACrossRefGoogle ScholarPubMed