Vitamin D modulation of innate immune signalling in Dendritic Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mahdad Noursadeghi
PROVIDER: E-MTAB-4883 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Identification of MEK-ERK or p38MAPK dependent genes in human monocyte derived dendritic cells. Dendritic cells (DC) promote tolerance or immunity depending on their maturation state. Previous studies have revealed that DC maturation is enhanced or accelerated upon MEK-ERK signaling pathway inhibition. We have now determined the contribution of MEK-ERK activation to the profile of gene expression of human immature monocyte-derived dendritic cells (MDDC) and peripheral blood myeloid DC. ERK inhibition altered the expression of genes that mediate CCL19-directed migration (CCR7) and LDL binding (CD36, SCARB1, OLR1, CXCL16) by immature DC. Besides, ERK upregulated CCL2 expression while impaired the expression of DC maturation markers (RUNX3, ITGB7, IDO1). MEK-ERK-regulated genes exhibited an over-representation of cognate sequences for the Aryl Hydrocarbon Receptor (AhR) transcription factor, and we show that AhR mediates some of the ERK-dependent transcriptional effects in DC. Therefore, MEK-ERK signaling pathway regulates antigen capture, lymph node homing and the acquisition of maturation-associated genes, and its contribution to the maintenance of the immature state of MDDC and myeloid DC is partly dependent on the activity of AhR. Since pharmacological modulation of the MEK-ERK signaling pathway has been proposed as a potential therapeutic strategy for cancer, our findings indicate that ERK inhibitors might influence the generation of anti-tumor responses through regulation of critical DC effector functions. Human peripheral blood monocytes from three independent healthy donors (DC4, DC5 and DC7) were isolated by anti-CD14-labeled magnetic microbeads. CD14+ monocytes were cultured for 5 days in RPMI 10% FCS containing GM-CSF and IL-4 to generate immature monocyte-derived dendritic cells (MDDC). Immature MDDC were exposed to MEK inhibitor, U0126, or p38MAPK inhibitor, SB203580 for 1 hour and a final dose of GM-CSF and IL-4 were added to the culture. Cells were collected for analysis after 4, 10 or 24 hours.Total RNA from each condition was extracted using the All prep DNA/RNA/protein mini kit (Qiagen) and hybridized to an Agilent Human Whole Genome (4x44) Oligo Microarray. All experimental procedures were performed following manufacturer instructions.
2013-05-03 | E-GEOD-39745 | biostudies-arrayexpress
Project description:Transcriptional response by macrophages stimulated with selected cytokines or innate immune stimuli
2016-02-09 | E-MTAB-3255 | biostudies-arrayexpress
Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1) Three two-condition experiments, control (N) vs tolerogenic DC with three different treatments. Pool of 4 indivuduals for each condition. One replicate per array.
2009-11-12 | E-GEOD-18921 | biostudies-arrayexpress
Project description:We used genome-wide transcriptional profiling by microarray to assess the contribution of pneumolysin on macrophage innate immune responses to the TIGR4 strain of Streptococcus pneumoniae (Spn). We focused on the early transcriptional responses at 4 hours after inoculation of human blood monocyte-derived macrophage cultures with Spn at a multiplicity of 10 bacteria to each cell. We compared transcriptomes in the presence and absence of wildtype or pneumolysin-deficient TIGR4 Spn, and also in the presence and absence of cytochalasin D to assess whether there is a differential effect of pneumolysin on innate immune responses with and without bacterial internalisation.
2021-03-31 | E-MTAB-8947 | biostudies-arrayexpress
Project description:Streptococcus Pneumoniae capsule is a major virulence factor. The capsule is known to inhibit complement fixation and phagocytes, but its impact on innate immune responses is not known. To address this question, we compared transcriptional responses by human monocyte derived macrophages in responses to wild type S. pneumoniae with isogenic mutant bacteria lacking their capsule. We conducted these experiments with and without macrophage pretreatment with cytochalasin D to evaluate the impact of phagocytosis, and we also made comparisons to mutant S.pneumoniae lacking bacterial lipoprotein which is known to be necessary for maximal innate immune responses.
2018-04-02 | E-MTAB-5894 | biostudies-arrayexpress
Project description:Allergic contact dermatitis (ACD) is the most prevalent form of immunotoxicity in humans. Dendritic cells (DC) play a central role in the pathogenesis of ACD, particularly during the sensitization phase to a specific allergen. Upon activation, DCs maturate and migrate to draining lymph nodes which is accompanied by major metabolic and phenotypic alterations that facilitate the presentation of the captured antigen to prime naïve T cells. Nevertheless, knowledge on the molecular effects during maturation of DCs in the context of ACD remain scarce. Here, we present a global proteomic analysis of monocyte-derived dendritic cells (MoDC) treated with NiSO4, the most prominent cause of ACD. Proteomic alterations induced after treatment with NiSO4 were compared to the bacterial trigger lipopolysaccharide (LPS). Both substances possess a similar TLR4 binding capacity, which may help to identify allergy-specific effects compared to bacterial activation. MoDCs treated for 24 h with 2.5 µg/ ml LPS displayed a very strong immunological response, characterized by upregulation of DC activation markers, secretion of proinflammatory cytokines and stimulation of T cell proliferation. Similar immunological responses were observed after treatment with 400 µM NiSO4 but less pronounced. Both triggered TLR4 and TREM1 pathways. However, NiSO4 in addition, also activated hypoxic and apoptotic pathways, which might have overshadowed initial signaling. Moreover, our proteomic data support the importance of Nrf2 as a key player in mediating sensitization since many Nrf2 targets genes were strongly upregulated on protein level selectively after treatment with NiSO4. Strikingly, NiSO4 stimulation induced cellular hypocholesterolemia which was counteracted by the induction of genes and proteins relevant for cholesterol biosynthesis. Our proteomic study allowed for the first time to better characterize some of the fundamental differences between NiSO4 and LPS-triggered activation of MoDCs, providing an important contribution to the molecular understanding of contact allergy.
2021-03-29 | PXD022599 | Pride
Project description:Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination. Experiment Overall Design: Transcriptional profiles of immature mo-DC (immDC, n=3), mature stimulatory mo-DC (matDC, n=3) and mature inhibitory mo-DC either stimulated with prostaglandin E2 (PGE2-DC, n=3) or infected with L.monocytogenes (infDC, n=3) were compared on Affymetrix HG-U133A platform. All samples represent biological replicates and were processed separately throughout the experiment.
2008-11-07 | E-GEOD-9946 | biostudies-arrayexpress
Project description:Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine. We analyzed the gene expression profiles of uninfected human monocyte-derived dendritic cells (MDDCs) and MDDCs infected with an envelope-defective GFP-encoding VSV-G-pseudotyped HIV-1 vector (HIVGFP(G)) and with VSV-G pseudotyped virus-like particles derived from SIVmac to deliver Vpx (SIVVLP(G)), alone or in combination. Cells were infected at day 4 of differentiation and cells were harvested 48 hours later. RNA was extracted with TRIzol. RNA was labeled and hybridized to Human Genome U133A 2.0 arrays arrays following the Affymetrix protocols. Data were analyzed in R and Bioconductor.
2010-09-09 | E-GEOD-22589 | biostudies-arrayexpress
Project description:The lineage relationships and fate of human blood and tissue dendritic cells (DC) has significance for a number of diseases including HIV where both blood and tissue DC may be infected. We used gene expression profiling of monocyte and DC sub-populations sorted directly from blood and skin and compared this to monocyte derived DC (MDDC) and MUTZ3 Langerhans cells (LCs) to define the lineage relationships. Hierarchical clustering analysis showed that plasmacytoid DCs formed the most discrete cluster. The ex vivo derived myeloid cells formed two separate clusters of cells derived from blood, and skin. Separate and specific DC populations could be determined within the sub-clusters. During overnight culture CD14+ dermal DCs (DDC) converted to CD1a+ expressing cells in situ consistent with origin of the CD1a+ DDC from a local precursor rather than from circulating blood DC or monocyte precursors. The in vitro derived MDDC and MUTZ3 populations grouped within the skin DC cluster and MDDCs clustered most closely to CD14+ DDC consistent with the proposed similarity between these two cell types. We identified differential expression of novel genes in particular DC subsets including genes related to DC surface receptors (including C-type lectin receptors, toll-like receptors and galectins). Total RNA was extracted and hybridised to 24 bead arrays. Dendritic cells and monocytes from human blood and skin using magnetic bead and flow cytometry based cell sorting both before and after culture for 24 hours
2011-12-01 | E-GEOD-32400 | biostudies-arrayexpress
Project description:The comparative analysis of the transcriptome of tolerogenic dendritic cells (tolDC) differentiated using different stimulus (either vitamin D3, dexamethasone or rapamycin) would allow to evidence potential common genes and pathways that could explain their potency as tolerance-inducing cells.
2018-07-31 | E-MTAB-6937 | biostudies-arrayexpress