Regulation of intestinal immune networks by the DNA motifs from probiotics.

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A great interest has increased concerning the therapeutic and preventive effects of yogurt against several diseases. Lactobacillus delbrueckii ssp. bulgaricus (L.bulgaricus) and Streptococcus thermophilus (S.thermophilus), which are dairy lactic acid bacteria (LAB), has been commonly used in yogurt production in the world. In our recent study, we have been particularly focusing on the DNA from yogurt starter cultures as one of the immunomoduratory factors in the LAB.The present study was conducted to elucidate the immunomoduratory functions of the DNA in the gut. The DNA from L.bulgaricus and S.thermophilus significantly stimulated mitogenic responses to murine peyer's patch cells and induced CD69 on the cells. The active DNA was cloned and the DNA motif, looks like CpG motif, was found in L.bulgaricus NIAI B6. L.bulgaricus NIAI B6 was passed through the M cells and digested by macrophage/dendritic cells result in the stimulation of immune cells by the DNA motif. The binding and ingestion of the DNA motif were demonstrated in peyer's patch cells. The DNA motif augmented induction of Th1 type cytokine (IL-7, IL-12, IL-18, IFNγ) mRNA in peyer's patches. Since swine will be valuable as a human model, swine IL-7 cDNA was isolated from neonatal intestinal epithelium by the RACE methods with designated primers based on the conserved sequences of the other mammalian IL-7. Cytokine producing cells induced by the DNA motif were detected in several immune cells such as B, NK, NKT and Dendritic cells. This study demonstrated that mucosal immunostimulatory DNA motif exist in L.bulgaricus NIAI B6 and proposed that the microorganism is a good candidate of a starter culture for the production of new functional foods, "Bio-Defense Foods".