Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development

Abstract

Dendritic cells (DC) are the main orchestrators of specific immune responses. Depending on microbial information they encounter in peripheral tissues, they promote the development of Th1, Th2 or unpolarized Th cell responses. In this study we have investigated the immunomodulatory effect of non-pathogenic intestinal Gram-negative (Escherichia coli, Bacteroides vulgatus,Veillonella parvula, Pseudomonas aeruginosa) and Gram-positive (Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum and Staphylococcus aureus) bacteria on human monocyte-derived DC (moDC). None of the Gram-positive bacteria (GpB) primed for Th1 or Th2 development. In contrast, despite the low levels of IL-12 they induce, all Gram-negative bacteria (GnB) primed moDC for enhanced Th1 cell development, which was dependent on IL-12 and an additional unidentified cofactor. Strikingly, GnB-matured moDC expressed elevated levels of p19 and p28 mRNA, the critical subunits of IL-23 and IL-27, respectively, suggesting that the IL-12 family members may jointly be responsible for their Th1-driving capacity. Purified major cell wall components of either GnB or GpB did not yield Th cell profiles identical to those obtained with whole bacteria, and could not explain the induction of the IL-12 family members nor Th1 priming by GnB. Importantly, this study gives indications that the expression of the different IL-12 family members is dictated by different priming conditions of immature DC.