Disease relevance of MDDC

• To better understand immune modulation by endotoxin and facilitate the development of novel vaccine adjuvants, the structural requirements of Neisseria meningitidis lipopoly(oligo)saccharide (LOS) for activation of human monocyte derived dendritic cell (MDDC) was determined [1].
• In contrast to Escherichia coli LPS, IL-5 production was enhanced or maintained in CD4+ T-cells stimulated with MDDC exposed to wild-type meningococcal LOS and KDO(2)-lipid A [1].
• Both normal and lupus MDDC are sensitive to nucleosome-induced activation [2].
• Exosomes from monocyte-derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8(+) T cells [3].
• RESULTS AND CONCLUSIONS: From recent work, it is clear that immature MDDC have a complex pattern of HIV gp120 binding [4].

High impact information on MDDC

• Moreover, activated MDDC secrete IL-8, a neutrophil chemoattractant also detected in patient sera, and thus might favor the inflammation observed in patients [2].
• To test this hypothesis, human MDDC were prepared by treating adherent monocytes with IL-4 and GM-CSF, and Mphi were produced by culture in M-CSF [5].
• Together, these data demonstrate differential expression of GPR105 on immature and mature MDDC and suggest a role for the receptor and its agonist ligand in DC activation [6].
• Although macrophages (Mphi) and monocyte-derived dendritic cells (MDDC) come from a common precursor, they are distinct cell types [5].
• Little or no expression was observed within the monocyte and mature MDDC cluster [6].

Chemical compound and disease context of MDDC

• Here we better define the impact of cyclic AMP (cAMP) intoxication due to the action of ACT on dendritic cell (DC)-driven immune response, by infecting monocyte-derived DC (MDDC) with an ACT-deficient B. pertussis mutant (ACT- 18HS19) or its parental strain (WT18323) [7].
• The inhibitory effect was not due to toxicity or visible change in membrane ruffles, but affects on cytoskeletal reorganization were evident in MDDC treated with relevant rottlerin concentrations during adhesion [8].

Biological context of MDDC

• MMF reduced the number of immature MDDC in culture, dose-dependently, by inducing apoptosis and inhibited their stimulatory activity on allogeneic lymphocytes [9].
• In contrast, MDDC matured in the presence of MMF showed a more marked decrease in the FITC-dextran uptake than mature MDDC cultivated without MMF and the phenomenon correlated with down-regulation of the MR expression [9].
• The effects on chemokine receptor gene expression were less evident in MDDC and only a transient down-regulation of weak intensity could be detected following stimulation with rIL-16 [10].
• We have studied the effect of mycophenolate mofetil (MMF), a new drug used in prevention of transplant rejection, on differentiation, maturation and allostimulatory activity of human monocyte-derived dendritic cells (MDDC) [9].
• Moreover, CD49d integrin up-regulation and MDDC maturation were prevented by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase, but were almost unaffected by the mitogen-activated protein/extracellular signal-related kinase kinase 1/2 inhibitor PD98059 [11].

Anatomical context of MDDC

• Therefore, we evaluated the ability of recombinant IL-16 (rIL-16) to regulate receptor expression and cytokine release in monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC) [10].
• The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non-phagocytic [12].
• MDDC were generated in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of MMF [9].
• To address this hypothesis, monocyte derived DC (MDDC) of patients with chronic or resolved acute HBV infection and healthy controls were studied phenotypically by FACS analyses and functionally by mixed lymphocyte reaction, ELISA, ELISpot and proliferation assays of MDDC cultures or co-cultures with an allogeneic HBc-specific Th cell clone [13].
• This limited susceptibility of cord MDDC to M-tropic HIV infection may be due to lower expression of CD4 and CCR5 on the cell membrane and higher production of MIP-1alpha and MIP-1beta [14].

Associations of MDDC with chemical compounds

• CD49d integrin expression was dependent on cell maturation, as its induction was abrogated by N:-acetylcysteine, which inhibits NF-kappaB activation and the functional and phenotypic maturation of MDDC [11].
• The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide-matured MDDC compared to exosomes from immature MDDC [3].
• CONCLUSION: The protocol based on the combination of proinflammatory cytokines and PGE2 is better for the induction of maturation of human MDDC in vitro than the protocol using LPS alone [15].
• Moreover, immature MDDC from some donors treated with UDP-glucose exhibit an increase in expression of the costimulatory molecule CD86, which correlates with the intensity of the UDP-glucose-induced calcium flux [6].
• CT, LT, dibutyryl-cyclic-3',5'-AMP, and Forskolin also dominantly inhibit interleukin 12 and tumor necrosis factor alpha production by MDDC in the presence of saturating concentrations of lipopolysaccharide [16].

Regulatory relationships of MDDC

• These data suggest that KDO linked to a fully acylated meningococcal lipid A is required for meningococcal endotoxin's immunostimulatory activity of human MDDC via TLR4/MD-2 and that different endotoxin structures influence Th responses mediated by MDDC [1].
• Immature monocytes-derived dendritic cells (MDDC) upregulate CD86 and HLA-DR expression and develop dendrites and veiled processes [17].
• Analysis of the profile of IFNA genes expressed in virus-stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed in PDC was broader, with some donor and stimulus-dependent variability [18].
• Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists [19].
• In line with these findings, supernatants from Mtb-infected MDDC induced IFN-gamma production by T cells and enhanced IL-18R expression, whereas supernatants from MDM failed to do that [20].

Other interactions of MDDC

• The latter was associated with a low pro-inflammatory cytokine production during mixed lymphocyte reactions and a cytokine balance in favour of IL-10 in contrast to human MDDC [21].
• With or without TNF-alpha, MDDC generated in cytokines were infected by macrophage and T cell-tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte-derived macrophages (MDM) [12].
• We adapted a protocol to derive AGM MDDC by culture in the presence of GM-CSF and IL-4 [21].
• CD38 is down-modulated during differentiation into immature MDDC and expressed again upon maturation [22].
• By means of bispecific Abs, we have dramatically enhanced gene transfer to monocyte derived DC (MDDC) by retargeting adenoviral (Ad) vectors to a marker expressed on DC, CD40 [23].

Analytical, diagnostic and therapeutic context of MDDC

• BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC [24].
• In parallel, cytokine secretion was determined by ELISA before and after MDDC activation [25].
• HBV infection of MDDC was studied by quantitative PCR [13].
• Phenotypic characteristics of MDDC and their endocytic activity were studied by flow cytometry [15].
• We sought factors associated with melanoma-specific clinical response following intradermal vaccination with autologous melanoma peptide and particulate hepatitis B antigen (HBsAg)-exposed immature monocyte-derived dendritic cells (MDDC) [26].

References