Modulation of Human DCs by a Lactobacillus Strain Figure 6. Expression levels of TLR signalling pathway in DCs treated with L. paracasei, Salmonella or both. Comparison of the expression of CASP8, TAK-1, JNK, IRF-3 and MAPK14 in DCs in the presence of the probiotic (Prob), its supernatant (CFS), Salmonella (S.typhi) or a combination. LPS, 20 ng/ml, was used as a positive control. The fold change (Fc) represents the ratio of the expression in treated DCs to the expression in control cells. The data shown are the mean values and SEM of three independent experiments. *p,0.05 compared to controls; #p,0.05 compared to S.typhi. doi:10.1371/journal.pone.0043197.g006 [44]. In line with several authors, our results revealed that the inhibition of TLR4 pathway blocked IL-8 production [45]. Perhaps most revealing is that the CFS can induce changes in gene expression in the intestine through some factors secreted by the probiotic bacteria. This effect is likely partly responsible for the beneficial effect of probiotics, as highlighted by other authors [40,46–49]. Our results also coincide with those of another recent study indicating that live probiotic bacteria affect the intestinal immune response, whereas secreted components exert anti- inflammatory effects in the gastrointestinal tract [50]. In conclusion, probiotic microorganisms can apparently exert immunoregulatory effects through the secretion of various bacterial compounds that are sensed by host PRRs. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and by the decrease in the production of a broad array PLOS ONE | www.plosone.org 8 August 2012 | Volume 7 | Issue 8 | e43197