Mechanism of Induction and Regulation of Gut Mucosal Immune Stimulation by non-Pathogenic bacteria

MALDONADO GALDEANO, C; DOGI, C, BIBAS BONET M.E.; CHAVES, S. AND PERDIGON, G.

Ñürnberg, Germany

Congreso; World Conference on Magic Bullets. Celebrating Paul Erlich`s 150th Birthday; 2004

Non-pathogenic bacteria include fermented food play an important role on the immune system stimulation. They are named probiotic bacteria and they include many acid bacteria (LAB), bifidobacteria and others. Many researches were done to demonstrate the beneficial effect on human health induced by the probiotic bacteria. Scientifical evidence showed that mucosal immune stimulation, as one of the most important property of these microorganisms considering that the oral tolerance is the main mechanisms developed by the immune cells associated to the gut (GALT), many questions must be answered to understand the mechanisms of the interaction with epithelial and immune cells by which these non-pathogenic bacteria can induce up and down regulation. Especially considering the complex network of signals in the intestinal microenvironment, between procariotic and eucariotic cells, that constitutes an effective barrier against foreign antigens. Thus the main question is addressed to answer if the behaviour of the hexogenous non-pathogenic bacteria on the GALT is different of the commensal bacteria. We demonstrated that some probiotic bacteria of the genous Lactobacillus, such as L. casei, L. acidophilus and L. delbrueckii subsp. bulgaricus induced mucosal immune stimulation by the following mechanisms: 1- They are able to contact with the immune cells associated to the gut. It was demonstrated using labelling fluorescent bacteria. 2- By transmission electronic microscopy (TEM) we observed that the non-pathogenic bacteria interact with the epithelial cells and only their antigenic particles, but not the whole of bacteria are able to internalize and make contact with the immune cells. 3- Such interaction with the immune cells induced the homming of immune cells and the induction of the IgA cycle with an increase of IgA+ cells in gut, bronchus and mammary gland. 4- We determined that also the interaction with immune cells associated to the gut induced an increase in proinflammatory (IFN, TNF, IL-12) and regulatory cytokines (IL-4, IL-10) favouring both innate and adaptative mucosal immune response. 5- The cellular homming induced from the gut mucose allowed to find an enhance in the cytokine release in distant site from the gut as it was observed in the spleen when we demonstrated an increase in TNF producing cells, at similar levels to those detected in Peyer’s patches for this cytokine. 6- We demonstrated that the signals induced on the immune cells led to express an increase in the receptor mannose on the cells of innate immunity favouring the antigenic presentation by other receptor than TCR. These results showed as that non-pathogenic bacteria are able to send more than one signals to activate and to enhance the immune response. 7- We found that the immune stimulation of commensal bacteria from the gut are less effective than the heterologous non-pathogenic bacteria even when we tested the same genous and specie, mean that the immune stimulation by these bacteria is a property specific of the strain. 8- We demonstrated that the mucosal immune cells activation is regulated at the gut level after long term of consumption and it is mediated by regulatory cytokine such as IL-10. 9- This down regulation was also observed at the bronchus associated lympho tissue (BALT). Conclusion: Non-pathogenic bacteria can have an immunomodulatory effect of the mucosal and immune response. The signals induced by these bacteria are different to those observed for pathogenic bacteria, where the inflammatory response is predominant. These studies are the scientifical basis for a better understanding of the interaction of non-pathogenic bacteria in a complex ecosystem as the gut. They open an important point of view for the use of these probiotic bacteria to improve the human health