IFNa DCs and IL4 DCs exposed to H1N1, heat killed S. aureus, or heat killed S. enterica (HKSE) for 1h, 2h, 6h, 12h, or 24h
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44720 | GEO | 2014/10/22
SECONDARY ACCESSION(S): PRJNA191088
REPOSITORIES: GEO
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2014-10-22 | E-GEOD-44720 | biostudies-arrayexpress
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2014-10-22 | GSE44719 | GEO
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2014-10-22 | GSE44721 | GEO
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2014-10-22 | E-GEOD-44721 | biostudies-arrayexpress
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines. 5 donors; 88 samples; duplicate technical replicates for the medium control for each donor for the BDCA1+ mDC population; single medium control for each donor for the BDCA3+ mDC population (15 total medium controls).
2014-10-22 | E-GEOD-56744 | biostudies-arrayexpress
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines.
2014-10-22 | GSE56744 | GEO
Project description:Background: Allergic asthma is one of the chronic inflammatory diseases and is generally induced by CD4+ T helper 2 cells (Th2) in the context of persistent inhaled stimuli. Dendritic cells (DCs) are essential to mounting the Th2-mediated airway inflammation by presenting inhaled antigens to prime CD4+ T cells. Small extracellular vesicles (sEV) derived from mesenchymal stem cells (MSCs) exhibited great interest in intractable diseases. However, whether MSC-sEV play a role on DCs in airway inflammation is still unclear. Methods: We isolate MSC-sEV using anion-exchange chromatography. Mouse bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs (moDCs) were used to study the effects of MSC-sEV on dendritic cell surface molecules and their cytokine release. Mice were sensitized with house dust mites (HDM) to induce airway inflammation, and treated with MSC-sEV, The effects of sEV on murine DCs were identified. Extracellular flux analysis techniques were used to study the effects of MSC-sEV on the metabolic state of dendritic cells. RNA sequencing to study altered gene expression in BMDCs after MSC-sEV treatment. Results: MSC-sEV mitigated the accumulation of Th2-associated moDCs in mouse lung in response to HDM. MSC-sEV also decreased the activation of moDCs induced in vitro including the expression of co-stimulatory molecules and cytokines secretion. Furthermore, we identified that DCs were able to take MSC-sEV in vitro and in vivo. Mechanistically, using bulk RNA-sequencing, we found that MSC-sEV played roles in the metabolic pathway of murine DCs. Using extracellular flux analysis, we found that MSC-sEV increased the requirement of oxidative phosphorylation on moDCs. Importantly, MSC-sEV displayed similar effects on human moDCs including decreased co-stimulatory molecular and cytokine production. Conclusions: MSC-sEV are able to alter the metabolic state of DCs, favoring DCs to maintain OXPHOS (oxidative phosphorylation) rather than glycolysis, thereby reducing DCs-initiated inflammatory responses and attenuating Th2 lung inflammation, suggesting MSC-sEV can be a potential clinical therapy for airway inflammation.
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Project description:Human dendritic cells play a fundamental role in the initiation of long-term adaptive immunity during vaccination against influenza. Understanding the early response of human DCs to vaccine challenge is thus essential to determine the nature and magnitude of maturation signals that strongly correlate with vaccine effectiveness. Here, we show that the non-adjuvanted trivalent Fluzone®09-10 (TIV-09) induces monocyte-derived DCs (moDCs), purified blood conventional DCs (cDCs) and plasmacytoid DCs (pDCs) to express CD80, CD83, and CD86, and secrete cytokines. TIV-09 stimulated the secretion of type I interferons (IFN) IFN-α and IFN-β and type III IFN IL-29 by moDCs and cDCs subsets. The vaccine also induced the production of IL-6, TNF and the chemokines IP-10 and MIP-1β. Conversely, the non-adjuvanted monovalent H1N1 California vaccine (MIV-09), which was commercialized in 2009 during the H1N1 epidemics and displayed lower effectiveness in retrospective studies, did not induce the production of type I IFN in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFN by these DCs. Yet, both vaccines induced pDCs to secrete type I IFN indicating that different influenza vaccines activate different molecular signaling pathways in different DC subsets. In vivo, the baseline IFN signature was decreased upon administration of the H1N1 vaccine in 3/3 pediatric lupus patients. These results suggest that subtypes of non-adjuvanted influenza vaccines elicit long-term protection through different mechanisms and that a vaccine’s ability to induce an IFN response in DCs may palliate the absence of adjuvant and increase vaccine efficacy.
2016-12-25 | GSE81691 | GEO
Project description:Human dendritic cells play a fundamental role in the initiation of long-term adaptive immunity during vaccination against influenza. Understanding the early response of human DCs to vaccine challenge is thus essential to determine the nature and magnitude of maturation signals that strongly correlate with vaccine effectiveness. Here, we show that the non-adjuvanted trivalent Fluzone®09-10 (TIV-09) induces monocyte-derived DCs (moDCs), purified blood conventional DCs (cDCs) and plasmacytoid DCs (pDCs) to express CD80, CD83, and CD86, and secrete cytokines. TIV-09 stimulated the secretion of type I interferons (IFN) IFN-α and IFN-β and type III IFN IL-29 by moDCs and cDCs subsets. The vaccine also induced the production of IL-6, TNF and the chemokines IP-10 and MIP-1β. Conversely, the non-adjuvanted monovalent H1N1 California vaccine (MIV-09), which was commercialized in 2009 during the H1N1 epidemics and displayed lower effectiveness in retrospective studies, did not induce the production of type I IFN in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFN by these DCs. Yet, both vaccines induced pDCs to secrete type I IFN indicating that different influenza vaccines activate different molecular signaling pathways in different DC subsets. In vivo, the baseline IFN signature was decreased upon administration of the H1N1 vaccine in 3/3 pediatric lupus patients. These results suggest that subtypes of non-adjuvanted influenza vaccines elicit long-term protection through different mechanisms and that a vaccine’s ability to induce an IFN response in DCs may palliate the absence of adjuvant and increase vaccine efficacy.
2016-12-25 | GSE81690 | GEO