Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation

• Published in: PloS one 2012-08, Vol.7 (8), p.e43197-e43197
• Main Authors: Bermudez-Brito, Miriam, Muñoz-Quezada, Sergio, Gomez-Llorente, Carolina, Matencio, Esther, Bernal, María J, Romero, Fernando, Gil, Angel
• Format: Article
• Language: English
• Subjects: Activation; Antigen-presenting cells; Antigens; Antigens, CD34 - biosynthesis; Bacteria; Biochemistry; Biology; Biomedical research; Bone morphogenetic proteins; Breast feeding; Caspase 8 - metabolism; CD34 antigen; Cell culture; Cells (biology); Chemokines; Chemokines - metabolism; Coculture Techniques; Cord blood; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - microbiology; Dendritic structure; Digestive system; Digestive tract; Food science; Functional foods; Functional foods & nutraceuticals; Gastrointestinal tract; Gene expression; Gene Expression Regulation, Bacterial; Genes; Health aspects; Hematopoietic stem cells; Humans; Immune response; Immune system; Immunity; Immunity, Innate - physiology; Immunological tolerance; Infants; Infections; Inflammation; Inflammatory diseases; Innate immunity; Intestine; Intestines - cytology; Intestines - microbiology; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Lactobacillus; Lactobacillus - metabolism; Lactobacillus acidophilus; Lactobacillus paracasei; Lamina propria; Langerhans cells; Microorganisms; Molecular biology; Monocytes; Nutrition; Probiotics; Probiotics - metabolism; Progenitor cells; Proteins; Salmonella; Salmonella - metabolism; Salmonella Infections - metabolism; Signal transduction; Signaling; Stem cell transplantation; Stem cells; Surface antigens; Toll-like receptors; Toll-Like Receptors - metabolism; Transcription; Transcription (Genetics); Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Transforming growth factors; Umbilical cord; Up-Regulation; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0043197

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.