Regulation of TLR4, p38 MAPkinase, IκB and miRNAs by inactivated strains of lactobacilli in human dendritic cells.

Strain specific properties of probiotics in providing supportive health effects in the immune system and the gastrointestinal tract have been widely investigated in vivo and in vitro. However, the underlying responsible mechanism is poorly described. By unravelling the probiotic-induced responses in a complex network of interacting signalling pathways, we investigated the effect of heat-inactivated Lactobacillus rhamnosus GG (LGG) and Lactobacillus delbrueckii subsp. bulgaricus (L.del) on the expression of TLR4 and signalling factors such as p38 MAPK and I?B at transcription level in human monocyte-derived dendritic cells (DCs). Our findings demonstrated that even inactivated probiotic strains can affect TLR4 expression in a down-regulatory direction as with lipopolysaccharides after 12 hours. LGG significantly down-regulated expression of p38 while I?B expression was significantly reduced in L.del-treated DCs. Moreover, we found these Lactobacillus strains could even modify the immune response at post-transcriptional level by modifying miRNAs expression. Based on our results LGG induced a significant down-regulatory effect on miR-146a expression which is known as a novel fine negative regulator of immune response targeting NFκB. On the other hand, miR-155 was up-regulated by LGG which is consistent with down-regulation of p38 and in LGG-treated DCs. These findings provide genetic and epigenetic explanations for the responsible underlying mechanisms by which probiotics influence immune response by targeting DCs.