Influenza Vaccines Differentially Regulate the Interferon Response in Human Dendritic Cell Subsets
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE81692 | GEO | 2016/12/25
SECONDARY ACCESSION(S): PRJNA322316
REPOSITORIES: GEO
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Project description:Human dendritic cells (DCs) 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 exposure is thus essential to determine the nature and magnitude of maturation signals that have been shown to strongly correlate with vaccine effectiveness. In 2009, the H1N1 influenza epidemics fostered the commercialization of the nonadjuvanted monovalent H1N1 California vaccine (MIV-09) to complement the existing nonadjuvanted trivalent Fluzone 2009-2010 vaccine (TIV-09). In retrospective studies, MIV-09 displayed lower effectiveness than TIV-09. We show that TIV-09 induces monocyte-derived DCs (moDCs), 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 (IFNs) IFN-? and IFN-? and type III IFN interleukin-29 (IL-29) by moDC and cDC subsets. The vaccine also induced the production of IL-6, tumor necrosis factor, and the chemokines IFN-?-inducible protein 10 (IP-10) and macrophage inflammatory protein-1? (MIP-1?). Conversely, MIV-09 did not induce the production of type I IFNs in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFNs by these DCs. However, both vaccines induced pDCs to secrete type I IFNs, indicating that different influenza vaccines activate distinct molecular signaling pathways in DC subsets. These results suggest that subtypes of nonadjuvanted influenza vaccines trigger immunity through different mechanisms and that the ability of a vaccine to induce an IFN response in DCs may offset the absence of adjuvant and increase vaccine efficacy.
| S-EPMC5484150 | biostudies-literature
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
Project description:Influenza Vaccines Differentially Regulate the Interferon Response in Human Dendritic Cell Subsets
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-22 | E-GEOD-44722 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-10-22 | GSE44722 | GEO
Project description:The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines.
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Project description:The skin accommodates multiple dendritic cell (DC) subsets with remarkable functional diversity. Immune reactions are initiated and modulated by the triggering of DC by pathogen-associated or endogenous danger signals. In contrast to these processes, the influence of intrinsic features of protein antigens on the strength and type of immune responses is much less understood. Therefore, we investigated the involvement of distinct DC subsets in immune reactions against two structurally different model antigens, E. coli beta-galactosidase (betaGal) and chicken ovalbumin (OVA) under otherwise identical conditions. After epicutaneous administration of the respective DNA vaccines with a gene gun, wild type mice induced robust immune responses against both antigens. However, ablation of langerin+ DC almost abolished IgG1 and cytotoxic T lymphocytes against betaGal but enhanced T cell and antibody responses against OVA. We identified epidermal Langerhans cells (LC) as the subset responsible for the suppression of anti-OVA reactions and found regulatory T cells critically involved in this process. In contrast, reactions against betaGal were not affected by the selective elimination of LC, indicating that this antigen required a different langerin+ DC subset. The opposing findings obtained with OVA and betaGal vaccines were not due to immune-modulating activities of either the plasmid DNA or the antigen gene products, nor did the differential cellular localization, size or dose of the two proteins account for the opposite effects. Thus, skin-borne protein antigens may be differentially handled by distinct DC subsets, and, in this way, intrinsic features of the antigen can participate in immune modulation.
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Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response
2016-07-01 | GSE62110 | GEO
Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response We take peripheral plasmablast and test its response to influenza vaccines at day 7 after vaccination. This array data set is for day 0 (before vaccines)
2016-07-01 | E-GEOD-62110 | biostudies-arrayexpress