Human Intestinal Dendritic Cells Decrease Cytokine Release against Salmonella Infection in the Presence of Lactobacillus paracasei upon TLR Activation

Abstract

Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs) are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs) and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells) harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS) decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR) signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.

The Effect of Lactobacillus acidophilus PTCC 1643 on Cultured Intestinal Epithelial Cells Infected with Salmonella enterica serovar Enteritidis

“…Our observation that L. acidophilus modulates TLR gene expression is in agreement with several studies conducted in Germany, Spain, and France [25,26,29]. …”

Safety and Immunomodulatory Effects of Three Probiotic Strains Isolated from the Feces of Breast-Fed Infants in Healthy Adults: SETOPROB Study

“…IL-12 also decreased in volunteers that received B. breve CNCM I-4035, whereas the anti-inflammatory index (IL-10/IL-12) increased in the group fed L. paracasei CNCM I-4034. Immunomodulation by these three probiotic strains has been reported in in vitro experiments by Bermudez-Brito et al [32,33]. These authors showed that L. paracasei CNCM I-4034, B. breve CNCM I-4035 and L. rhamnosus CNCM I-4036 inhibited the production of pro-inflammatory cytokines and chemokines by human intestinal dendritic cells challenged with pathogenic bacteria and that such an effect seems to be mediated through a decreased expression of toll-like receptor (TLR)-1, TLR-5 and TLR-9 [32,33].…”

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

“…We speculate that the observed reduction in IL-1β-induced IL-6 secretion in H4 cells after exposure to live L. rhamnosus GG or SpaC may result from modulation of the common TLR and IL-1 receptor signaling pathway. Probiotic lactobacilli have been observed to modulate TLR gene expression and induce the expression of the TLR/IL1R interacting protein TOLLIP and immunoregulatory cytokines in human cord blood-derived dendritic cells (16). We have previously reported that secreted products from probiotic lactobacilli and bifidobacteria down-regulate TLR2 and TLR4 expression and attenuate inflammatory responses through a TOLLIP-dependent mechanism in the immature human gut (17).…”