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

摘要

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-1β 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.