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B bifidum actively changes the gene expression profile induced by L acidophilus in murine dendritic cells

ABSTRACT: Dendritic cells (DC) play a pivotal regulatory role in activation of the innate as well as the adaptive part of the immune system by responding to environmental microorganisms. We have previously shown that some lactobacilli strains induce a strong production of the pro-inflammatory and Th1 polarizing cytokine IL-12 in DC. Contrary, bifidobacteria do not induce IL-12, but are able to inhibit the IL-12 production induced by lactobacilli. In the present study, genome wide microarrays were used to investigate the maturation and gene expression pattern murine bone marrow derived DC stimulated with Lactobacillus acidophilus NCFM and Bifidobacterium bifidum Z9. L. acidophilus NCFM strongly induced expression of interferon (IFN)-β, multiple virus defence genes, and cytokine and chemokine genes related to both the adaptive and the innate immune response. Contrary, B. bifidum Z9 mostly up-regulated genes encoding cytokines and chemokines related to the innate immune response. Moreover, B. bifidum Z9 inhibited the expression of the genes initiating the adaptive immune response induced by L. acidophilus NCFM and had an additive effect on genes of the innate immune response and some Th2 skewing genes. The gene encoding Jun dimerization protein 2 (JDP2), a key regulator in cell signalling, was one of the few genes only induced by B. bifidum Z9. Blocking of the JNK1/2 pathway completely inhibited the gene expression of Ifn-β. We suggest that B. bifidum Z9 employs an active mechanism to inhibit induction of genes in DC triggering the adaptive immune system and that JPD2 is involved in the regulatory mechanism.

ORGANISM(S): Mus musculus

PROVIDER: GSE20302 | GEO | 2010/02/13

SECONDARY ACCESSION(S): PRJNA125339

REPOSITORIES: GEO

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Project description:Lactobacilli are probiotics that, among other health promoting effects, have been ascribed immunostimulating and virus preventive properties. Certain lactobacilli species have been shown to possess strong IL-12 inducing properties. As IL-12 production depends on the up-regulation of type I interferons, we hypothesized that the strong IL-12 inducing capacity of L. acidophilus NCFM in murine bone marrow derived DC is caused by an up-regulation of IFN-Î², which subsequently stimulates the induction of IL-12 and the dsRNA binding toll like receptor (TLR)-3. The expression of the genes encoding IFN-Î², IL-12, IL-10 and TLR-3 in DC upon stimulation with L. acidophilus NCFM was measured. L. acidophilus NCFM induced a much stronger expression of ifn-Î², il-12 and il-10 compared to the synthetic dsRNA ligand Poly I:C, whereas the levels of expressed tlr-3 were similar. By the use of whole genome microarray gene expression, we investigated whether other genes related to the viral defence were up-regulated in DC upon stimulation with L. acidophilus NCFM and found that various virus defence related genes, both early and late, were among the strongest up-regulated genes. The IFN-Î² stimulating capability was also detected in another L. acidophilus strain, but was not a property of other probiotic bacteria tested (B. bifidum and E. coli nissle).The IFN-Î² inducing capacity was markedly reduced in TLR-2 -/- DCs, dependent on endocytosis and the major cause of the induction of il-12 and tlr-3 in L. acidophilus NCFM stimulated cells. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DC in a TLR-2 manner through induction of IFN- Î². Experiment Overall Design: In the experiment Lactobacillus NCFM were added to murine dendritic cells and stimulated for 4, 10 or 18 hours. These were compared to control experiment at the same timepoints. Experiments were run in triplicates except for control 10h and control 18h which were only in duplicate, giving a total of 16 arrays.

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B bifidum actively changes the gene expression profile induced by L acidophilus in murine dendritic cells

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