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Dendritic cells (DCs) constitute the first point of contact between gut commensals and our immune system. Despite growing evidence of the immunomodulatory effects of probiotics, the interactions between the cells of the intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of this work was to determine whether the probiotic  Bifidobacterium breve  CNCM I-4035 and its cell-free culture supernatant (CFS) have immunomodulatory effects in human intestinal-like dendritic cells (DCs) and how they respond to the pathogenic bacterium  Salmonella enterica  serovar  Typhi , and also to elucidate the molecular mechanisms involved in these interactions. Human DCs were directly challenged with  B. breve /CFS,  S. typhi  or a combination of these stimuli for 4 h. The expression pattern of genes involved in Toll-like receptor (TLR) signaling pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with  S. typhi . In contrast, the  B. breve  CNCM I-4035 probiotic strain was a potent inducer of the pro-inflammatory cytokines and chemokines tested, i.e., TNF-α, IL-8 and RANTES, as well as anti-inflammatory cytokines including IL-10. CFS restored TGF-β levels in the presence of  Salmonella . Live  B.breve  and its supernatant enhanced innate immune responses by the activation of TLR signaling pathway. These treatments upregulated  TLR9  gene transcription. In addition, CFS was a more potent inducer of  TLR9  expression than the probiotic bacteria in the presence of  S. typhi . Expression levels of  CASP8  and  IRAK4  were also increased by CFS, and both treatments induced  TOLLIP  gene expression. Our results indicate that the probiotic strain  B. breve  CNCM I-4035 affects the intestinal immune response, whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This supernatant may protect immune system from highly infectious agents such as  Salmonella typhi  and can down-regulate pro-inflammatory pathways.

plos one

Cell-Free Culture Supernatant of Bifidobacterium breve CNCM I-4035 Decreases Pro-Inflammatory Cytokines in Human Dendritic Cells Challenged with Salmonella typhi through TLR Activation