Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease

Abstract

SummaryInflammatory bowel disease (IBD) results from a breakdown of tolerance towards the indigenous flora in genetically susceptible hosts. Failure of dendritic cells (DC) to interpret molecular microbial patterns appropriately when directing innate and adaptive immune responses is conceivable. Primary (conventional, non-monocyte generated) CD1c necrosis factor (TNF)-a and interleukin (IL)-8. Toll-like receptor (TLR)-4 expression by mDC was higher inremission and increased significantly in flaring UC and CD patients compared with remission (P < 0·05) and controls (P < 0·001). Fluorochrome-labelled LPS uptake by mDC was evaluated at different time-points over 24 h by measuring mean fluorescence intensity (MFI). Circulating mDC from IBD patients take up more LPS and the uptake begins earlier compared with controls (P < 0·05 in CD-FU and UC-FU at 24 h). The frequency of mucosal mDC (P < 0·05) and the number of CD40 expressing mucosal mDC is significantly greater in UC and CD compared with non-IBD controls (P < 0·001 versus P < 0·01, respectively). Our data suggest an aberrant LPS response of mDC in IBD patients, resulting in an inflammatory phenotype and possibly intestinal homing in acute flares.

Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation

“…Therefore, dysregulated function of innate immune cells that are responsible for phagocytosis of ACs (efferocytosis), such as macrophages and dendritic cells (DCs), could augment IBD pathogenesis. Intriguingly, IBD patients display higher frequencies of DCs positive for several activation and maturation markers in the lamina propria of inflamed colon tissues, and IBD DCs produce significantly more proinflammatory cytokines than DCs from healthy controls (11)(12)(13). Although these studies indicate that DCs have a function in IBD pathogenesis, their role in the inflammatory cascade leading to intestinal inflammation, and its association with AC clearance, has not been fully elucidated.…”

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

“…The number of DCs expressing the maturation markers CD80, CD83, CD86 and CD40 is elevated in CD and UC [102][103][104][105]. DCs express also higher levels of TLR2 and TLR4 [102] and accordingly, show exaggerated response to LPS in IBD [106]. This may result in false recognition of commensal bacteria and induction of pro-inflammatory immune responses.…”

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

“…Co-expression of CD103 was found on approximately 4% of the cells. A similar population was identified by Baumgart et al [35] as being CD14 -CD19 -CD11c + CD1c + . It is difficult to know if these cells correspond to migratory or tissue resident phagocytes since they express the migratory molecule CCR7 but few express CD103.…”

“…Consistent with this, Ng et al [54] showed that DCs from patients with Crohn's Disease express more IL-12p40 and IL6 compared to healthy controls. Finally, LPS stimulation of mucosal DCs in Crohn's Disease patients induced high secretion of TNFα and IL-8 [35]. For macrophages, it has been shown that CD14 + intestinal macrophages from patients with Crohn's Disease produced abundant IL-23 and TNF-α in response to stimulation with commensal bacteria [32].…”