Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model
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ABSTRACT:
PROVIDER: PRJNA390967 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection induced metabolic dysregulation and inflammatory responses, and also affected the immune cell content of the spleen and liver. Use of the mast cell stabilization drug, ketotifen, reversed many of these responses, and induced additional changes in the transcriptome and immune cell repertoire that contribute to decreased dengue disease.
2017-06-20 | GSE100195 | GEO
Project description:In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection induced metabolic dysregulation and inflammatory responses, and also affected the immune cell content of the spleen and liver. Use of the mast cell stabilization drug, ketotifen, reversed many of these responses, and induced additional changes in the transcriptome and immune cell repertoire that contribute to decreased dengue disease.
2017-06-20 | GSE100194 | GEO
Project description:There are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage, and shock due to the ability of DENV to infect a variety of immune and nonimmune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs), and infected monocytes, can contribute to immune pathology. In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection strongly induced metabolic dysregulation, complement signaling, and inflammation. DENV also affected the immune cell content of the spleen and liver, enhancing NK, NKT, and CD8+ T cell activation. The MC-stabilizing drug ketotifen reversed many of these responses without suppressing memory T cell formation and induced additional changes in the transcriptome and immune cell composition of the spleen, consistent with reduced inflammation. This study provides a global transcriptional map of immune activation in DENV target organs of an immunocompetent host and supports the further development of targeted immunomodulatory strategies to treat DENV disease.IMPORTANCE Dengue virus (DENV), which causes febrile illness, is transmitted by mosquito vectors throughout tropical and subtropical regions of the world. Symptoms of DENV infection involve damage to blood vessels and, in rare cases, hemorrhage and shock. Currently, there are no targeted therapies to treat DENV infection, but it is thought that drugs that target the host immune response may be effective in limiting symptoms that result from excessive inflammation. In this study, we measured the host transcriptional response to infection in multiple DENV target organs using a mouse model of disease. We found that DENV infection induced metabolic dysregulation and inflammatory responses and affected the immune cell content of the spleen and liver. The use of the mast cell stabilization drug ketotifen reversed many of these responses and induced additional changes in the transcriptome and immune cell repertoire that contribute to decreased dengue disease.
| S-EPMC5571258 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-20 | GSE100196 | GEO
Project description:Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model [spleen]
| PRJNA390971 | ENA
Project description:Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model [liver]
| PRJNA390972 | ENA
Project description:These 40 microarray datasets represent whole blood samples from 31 primary dengue infection patients and 9 healthy volunteers from Managua, Nicaragua. The dengue infection patients include both primary dengue fever (DF) and primary dengue hemorrhagic fever (DHF) cases.
2018-07-31 | GSE96656 | GEO
Project description:Mast cells are phenotypically and functionally highly heterogeneous, and their state is possibly controlled by their local microenvironment. Therefore, concrete analyses are needed to understand whether mast cells act as powerful motivators or dispensable bystanders in specific diseases. Here, we evaluated the correlation between synovial mast cells and rheumatoid arthritis (RA) disease severity, and the efficacy of therapeutic interventions against mast cells. We showed that degranulation of mast cells in inflammatory synovial tissues of RA patients was induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II (MHC II) and costimulatory molecules on mast cells were upregulated. These unique signaling response led to mast cell activation and promoted T cell responses, resulting in the progression of RA. Collagen-induced arthritis mouse models treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, showed significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to RA and may provide a novel mast cell-targeting therapy for RA.
2024-01-07 | PXD038584 | Pride
Project description:Dengue virus is an + strand RNA virus. We have carried our infections of human cells with Dengue and analyzed the translation, replication, and localization of the Dengue RNA. This allowed for clear definition of the life cycle of the Dengue virus inside a host cell. We also assessed the host response to Dengue virus, finding that a large fraction of the translational response is due to Interferon function. Translational and transcriptional analysis of the cellular response to Dengue virus infection
2016-09-01 | E-GEOD-69602 | biostudies-arrayexpress