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, Enteroccocus 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.

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

“…The canonical pathway, involved in innate immunity, is activated by proinflammatory stimuli, including TNF-a, various interleukins, microbes, and virus-related ligands. 47 Based on its close structural similarity with the viral oncoprotein v-Rel, the link between the NF-kB pathway and cancer was first suspected in 1990. 48 In the past decade, an increasing number of studies have shown that many cancers have constitutively active NFkB, including lung, colon, pancreatic, and ovarian cancers.…”

Expression of IL-23, VEGF and TLR2/TLR4 on Mononuclear Cells after Exposure to Pseudomonas Aeruginosa

“…IL-23 is essential for chronic inflammatory diseases and may be responsible for multiorgan inflammation (23). Several studies involving different infection models demonstrate that IL-23 can be induced in response to bacterial stimuli in human monocytederived dendritic cells (24) and macrophages (25), and contribute to the development of septic shock (10). Although IL-23 acts as an innate defense mechanism, it might contribute to exacerbating the inflammatory reaction, while, at a later stage, it may exert complex action on different cell types of the immune reactivity (10) .…”

Dendritic cells and cytokines in human inflammatory and autoimmune diseases

“…IL-23 is secreted by human DCs exposed to gram-negative bacteria [101]. As mentioned above, IL-23 promotes the development and expansion of activated CD4 + T cells that produce IL-17, IL-17F, IL-6 and TNF and are called Th17.…”