The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells...

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain more insights into the underlying mechanisms, in the present study, we analysed the modulation of bone marrow-derived dendritic cells (BM-DC) from BALB/c (T helper (Th)2 biased) v. C57BL/6 (Th1 biased) mice. Our findings showed that VSL#3 differed from pure Toll-like receptor (TLR) ligands by inducing the production of various cytokines, including IL-12 p70 subunit (IL-12p70), IL-23 and IL-10. Dedicated TLR arrays were employed to profile mRNA from BM-DC cultured with lipopolysaccharide (LPS), VSL#3, or a combination of both. This approach led to the identification of (1) a cluster of genes that were up- or down-regulated, irrespective of the stimulus, (2) a cluster of genes that were synergistically up-regulated by LPS and VSL#3 in BM-DC from C57BL/6 mice, but not in those from BALB/c mice, and (3) a cluster of LPS-induced genes that were suppressed by VSL#3, in particular chemokine genes. These data show that this probiotic mixture has both pro- and anti-inflammatory effects on BM-DC and suggest that their immune-modulating properties in vivo may depend on the genetic background of the host.