Modulation of Human DCs by a Lactobacillus Strain Figure 2. Measure of anti-inflammatory cytokines and TNF-a in DCs after exposure to L. paracasei, Salmonella or both. DCs were incubated with the probiotic L. paracasei CNCM I-4034 (Prob) or its cell-free supernatant (CFS), Salmonella (S.typhi), or both. IL-10, TNF-a, TGF-b1 and TGF-b2 production was measured. LPS, 20 ng/ml, was used as a positive control. Negative-control cultures contained unstimulated DCs. 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; N.D indicate no detected. doi:10.1371/journal.pone.0043197.g002 species can be classified as either immunostimulatory or immu- nomodulatory. Consistent with this work, L. paracasei CNCM I- 4034 and its supernatant appear to be immunomodulatory and could be used to dampen inflammatory responses [31]. Interestingly, the culture supernatant by itself could decrease Salmonella-induced inflammation. Indeed, these data suggest that L. paracasei CNCM I-4034 releases some factors of unknown nature, most likely bacteriocins, because the supernatants did not produce large changes in the profiles of the cytokines released by DCs in the absence of the enteropathogen. Accordingly, it is also important to note that this supernatant is concentrated tenfold, as is any other substance present in the growth medium. We suggest that it is unlikely that this inhibition is caused by growth- derived acidic compounds, such as lactic or acetic acid, because the supernatant used was neutralised to a pH of 7.0. Therefore, the nature of the soluble mediator released by L. paracasei CNCM I-4034 remains to be determined. It is clear that the exposure of DCs to pathogen and probiotic resulted in the release of TGF-b, an anti-inflammatory cytokine. L. paracasei CNCM I-4034 promoted the stimulation of TGF-b2, PLOS ONE | www.plosone.org 4 August 2012 | Volume 7 | Issue 8 | e43197