INTERACTION BETWEEN INTESTINE AND IMMUNE SYSTEM

MALDONADO GALDEANO CAROLINA; DE MORENO DE LEBLANC ALEJANDRA; VINDEROLA GABRIEL; PERDIGÓN GABRIELA

MEXICO

Simposio; 4º Simposio Internacional de Probióticos; 2006

Introduction. Lactobacilli, other microorganisms probiotics and fermented milks are known for their health promoting effects. Lactic acid bacteria (LAB) are the microorganism more used as probiotic, however not all the genus and or species of different LAB exhibit immunomodulatory properties. Probiotic bacteria can enhance the systemic and mucosal immune response, being the effect more remarkable at intestinal level. The mechanisms of the probiotic bacteria to induce gut mucosal immune stimulation are not well understood. It could speculate that the efficient activation of specific transcriptional factors by LAB would lead to fast and effective immune response. However many researches are still necessary to understand how the interaction of probiotic bacteria with the gut cells (epithelial or immune cells) initiate the complex network of signals to induce the immune response. Other critical aspects to consider are the mechanisms involved in the immune stimulation reached by fermented milks and if whether or not they are similar to those described for a single probiotic strain. It is also important to know the role in the immune stimulation exerted by the bacteria free fraction obtained after fermentation. Results and discussion. Scientific evidences, that we obtained using a murine model and testing different probiotic lactobacilli strains showed that: 1) the whole cells of probiotic bacteria are able to interact with the gut epithelial cells and their fragments can internalize and contact with the immune cells; 2) the epithelial cells are able to produce mainly IL-6; 3) after that probiotic bacteria contact dendritic cells (DC) or macrophages through their membrane receptors, they release inflammatory and regulatory cytokines to maintain intestinal homeostasis; 4) the increase in the number of IgA+ cells is not correlated with an increase of T population (CD4 or CD8); 5) the viability of administered bacteria is important for a better probiotic stimulation; 6) Antibodies specific against the probiotic bacteria were not found. Regarding the mechanisms involved in the immune stimulation by fermented milks; using a fermented milk by Lactobacillus helveticus and its bacteria free fraction 1) increases in the number of IgA+ and CD4+ cells; 2) both products but not single L. helveticus induced an increase in calcium channel in duodenum, and in the expression of calcineurin in macrophages, T and B cells; 3) an enhancement in the release of IL-2 and TNFa; 4) the barrier mechanisms such as the goblet cells (mucus producer cells), were also increased. Conclusions. We demonstrated for the single probiotic strain, Lactobacillus casei CRL 431, that the main mechanism involved in the immune stimulation is through the innate immunity. The fermented milk exerted an effect in cells involved in the gut non-specific barrier and increased the level of calcineurin able to activate transcriptional factors that mediate innate and specific immune response. References: Perdigón, G., Maldonado Galdeano C, Valdez, JC. and Medici M. (2002) Interaction of lactic acid bacteria with the gut immune system Eur. J. Clin. Nutr.Vol(56) Suppl 4, pp. S21-S26. Perdigón, G., Maldonado-Galdeano, C., de Moreno de LeBlanc, A., Vinderola, C.G., Medici, M. and Bibas Bonet, M.E. (2004).Immunomodulation of mucosal immune response by probiotics. Curr. Trends Immunol.Vol. (6) 69-85. Galdeano, C.M. and Perdigón, G. (2005). Role of viability of probiotic strains in their persistence in the gut and in mucosal immune stimulation. J. App. Microbiol. Vol (97)(4): 673-681. de Moreno de LeBlanc, A; Maldonado Galdeano, C; Chaves, S and Perdigón, G. (2005). Oral administration of L. casei CRL 431 increases immunity in bronchus and mammary glands. Eur. J. Inflam. Vol 3(1) 25-30. Vinderola, C.G., Matar, C. and Perdigón, G. (2005). Role of intestinal epithelial cells in the immune effects mediated by gram (+) probiotic bacteria. Involvement of toll-like receptors. Clin. Diag. Lab.Immunol.Vol (12): 1075-1084. Maldonado Galdeano C, Perdigón G. (2006). The Probiotic Bacterium Lactobacillus casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity. Clin Vaccine Immunol. Vol. (13) (2):219-26.