title: Selected commensal-related bacteria and Toll-like receptor 3 agonist combinatorial codes synergistically induce interleukin-12 production by dendritic cells to trigger a T helper type 1 polarizing programme.
abstract: Enteric infections remain a major health problem causing millions of deaths in developing countries. The interplay among the host intestinal epithelium, the mucosa-associated immune system and microbiota performs an essential role in gut homeostasis and protection against infectious diseases. Dendritic cells (DCs) play a key role in orchestrating protective immunity and tolerance in the gut. The mechanisms by which DCs adapt their responses and discriminate between virulent microbes and trillions of innocuous bacteria remain ill-defined. Here we investigated the effect of cross-talk between commensal-related bacteria (CB) and Toll-like receptor (TLR) agonists on DC activation and the outcome of the in vitro T helper response. Human monocyte-derived DCs were exposed to eight different Gram-positive or Gram-negative CB strains prior to activation with five different TLR agonists. The key polarizing cytokines interleukin (IL)-12p70, IL-10, IL-1beta and IL-6 were quantified and the fate of naïve T-cell differentiation was evaluated. We identified a unique combination of Lactobacillus casei and TLR3 signals that acted in synergy to selectively increase IL-12p70 secretion. Exposure to poly(I:C) converted L. casei-treated DCs into potent promoters of T helper type 1 (Th1) responses. We propose that DCs can integrate harmless and dangerous non-self signals delivered by viral products, to mount robust Th1 responses. Thus, in vivo DC targeting with selective probiotics may improve strategies for the management of enteric diseases.
authors.affiliation: Immunoregulation Laboratory, CRCHUM, University of Montreal, Montreal, QC, Canada.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Baba
authors.forename: Sandrine
authors.initials: S
authors.lastname: Samson
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Bourdet-Sicard
authors.forename: Manuel
authors.initials: M
authors.lastname: Rubio
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005408:Flagellin / Q000276:immunology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000819:agonists / Q000096:biosynthesis* / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D007780:Lacticaseibacillus casei / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D019936:Probiotics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000378:metabolism
chemical_list: D007369:Interferon Inducers; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D005408:Flagellin; D016753:Interleukin-10; D018664:Interleukin-12; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C