CENTRO DE REFERENCIA PARA LACTOBACILOS
Unidad Ejecutora - UE
Activation of the innate immunity by probiotic bacterium and a fermented milk containing this microorganism
MALDONADO GALDEANO, CAROLINA; DE MORENO DE LEBLANC, ALEJANDRA; DOGI, CECILIA; CHAVES, SILVINA; CARMUEGA, ESTEBAN; WEILL, RICARDO; PERDIGÓN, GABRIELA.
Proceeding of the Nutrition Society
Cambridge University Press
Año: 2008 vol. 67
The improvement of the immune status of the host is one of the beneficial properties attributed to the probiotics. Previous results in our laboratory showed that the effect induced by a probiotic strain Lactobacillus casei CRL 431was through the innate immunity. In the present work we analyze the behavior of the other probiotic bacterium Lactobacillus casei DN 114001 on the interaction with the epithelial and immune cells, using mice as experimental model. We demonstrated, by electron microscopy and fluorescent bacteria, which this bacterium interacts with the intestinal epithelial cells and the small fragments of the bacterium, can internalize and make contact with the immune cells (macrophages and dendritic cells) present in Peyer patches and in lamina propria of the small and large intestine. The permanence of these antigenic particles in the gut was 72 hours similar to the any particulate antigens. Since the results obtained, we studied the effect of this probiotic bacterium included in a fermented milk on the innate mucosal immune system of the gut BALBc mice. The fermented milk was administered to the mice during 5 consecutive days previously determined as optimal dose to stimulate the immune response. At the end of the administration period the animals were sacrificed and the small and large intestine was removed for the following studies: a) Determination of the number of IgA and the cytokines (IL-10, IFNg, TNFa) producing cells in histological slices of both intestines. b) The expression in the lamina propria of the small intestine of the different receptors present in the immune cells involved in the innate immunity, such as, mannose receptor CD206 present in macrophages or DC surface, this receptor participates mainly in the internalization and in the antigens clearence. We also studied TLR4, because this receptor is involved in the adhesion and proinflammatory signals induced by pathogenic bacteria as a way to measure possible adverse effects. We demonstrated increases in the number of IgA, TNFa and IFNg producing cells in both intestines. The antiinflammatory cytokine IL-10 also showed a significant increase in relation to the control without fermented milk administration. This increase may be was induced to down regulate the mucosal response. We also observed a slight increase in the receptor CD-206 while TLR4 was not increased. These results showed the implicance of the innate immunity in the gut mucosal immune activation observed and led us to investigate the influence of the consumption of this fermented milk in early period of the life where the maturation of the innate immune cells occurs. After weaning, newborn mice received the fermented milk until the adulthood (45 days). The number of the positive cells with the maturation markers, such as, F4/80+ cells (macrophages) and 33D1+ cells (dendritic cells) were determined in the small intestine. An increase in the expression of these markers in treated animals compared with the control group (newborn mice without fermented milk administration) was observed. These results demonstrated that the probiotic bacteria or their fragments interact with the epithelial and with the phagocytic immune cells in the gut. This observation would be related with the results obtained with the fermented milk assayed which increased the number of CD-206 receptor and activate the immune cells associated to the gut with an increase in the cytokine and IgA+ producing cells. The results observed for adults mice (45 days) that received the fermented milk after weaning, agree with the previous studies. We demonstrated that this fermented milk containing the probiotic strain L .casei DN 114001 can modulated the gut immune response mainly through the innate immunity by enhancing in the receptors related with the maturation of the macrophages and dendritic cells associated to the gut, by activating of these cells and by increasing in the number of IgA+ B cells.