Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation.
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.
Institute of Nutrition and Food Technology José Mataix, Biomedical Research Centre, Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain.
Miriam
M
Bermudez-Brito
Sergio
S
Muñoz-Quezada
Carolina
C
Gomez-Llorente
Esther
E
Matencio
María J
MJ
Bernal
Fernando
F
Romero
Angel
A
Gil
D018952:Antigens, CD34 / Q000096:biosynthesis; D053181:Caspase 8 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007249:Inflammation; D007422:Intestines / Q000166:cytology* / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007778:Lactobacillus / Q000378:metabolism*; D019936:Probiotics / Q000378:metabolism; D012475:Salmonella / Q000378:metabolism*; D012480:Salmonella Infections / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
D018952:Antigens, CD34; D018925:Chemokines; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C410602:TOLLIP protein, human; D051193:Toll-Like Receptors; D053773:Transforming Growth Factor beta1; D053181:Caspase 8