Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215835 | GEO | 2023/04/13
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Dengue virus (DENV) infection often leads to acute illness lasting 2-7 days with severity ranging from dengue fever (DF) to hemorrhagic fever (DHF) and fatal dengue shock syndrome (DSS). The dynamic changes of host responses on the gene transcription level that accompany DENV infection and differences between DF and DHF cases have been poorly understood, particularly for South American population. Methodology/Principal Findings: Supported by a longitudinal active surveillance program for dengue transmission in Maracay, Venezuela, we conducted a prospective study to investigate host responses in dengue patients. Blood specimens and clinical information were collected on a daily basis from febrile cases confirmed with DENV infection from their first day of enrollment to early defervescence together with one convalescent sample. A total of 49 and 13 study participants were defined as DF and DHF cases respectively based on their clinical and hematological information. Using convalescent specimens as baseline, day-to-day gene expression was evaluated ex vivo in peripheral blood mononuclear cells of the study participants. Two waves of gene expression were detected: the first wave peaked at day 1 from the onset of fever (day 0) then declined at days 3-4; the second wave emerged from day 4 and peaked around day 5-6. Genes associated with innate immune process, including type I interferon signaling, cytokine-mediated signaling, chemotaxis, and antiviral responses, dominated the first wave; whereas genes involved in cell cycle processes, including cell division, mitosis, DNA replication, chromosome, and spindle organization dominated the second wave. Measureable genomic markers predicted early acute, late acute and convalescent phases with 91% accuracy. Gene signatures expressed in early acute phase predicted disease severity (DF vs DHF) with 96% accuracy. Conclusions/Significance: Our study established a dynamic pattern of detailed host immune responses to DENV infection and revealed genomic signatures valuable for diagnostics purposes. Total 64 subjects representing 51 DF (dengue fever) and 13 DHF (dengue hemorrhagic fever) cases were used to study gene expression during the course of dengue acute illness. Sample information regarding Patient No., Infecting serotype, fever status (fever days or defervescent (df) days), and disease severity (DF vs DHF) were provided. The date for a sample for gene chip hybridization and image scanning was marked as Scan date. Samples from study subjects were collected once a patient was enrolled. Over 200 samples were collected. Two genechip platforms were used, the HG-focus and HG-U133plus2. A total of 168 samples were assayed on the HG-focus platform, 2 were excluded for further analysis as they failed on quality control (i.e. VFP-0003_G7_DF, VFP-0029_G1_DF samples). A total of 101 samples were assayed on the HG-U133plus2 platform, 4 were excluded for further analysis as they failed on quality control (i.e. VFP_0186_G4_DF, VFP-0213_G3_DF, VFP_0213_G5_DF, VFP_0220_G3_DHF). Data generated by HG-focus platform were used to explore significantly expressed genes in individual Gs, phases, and for prediction analysis for disease phases. Whereas data generated by HG-U133plus2 were first used to assess the reproducibility of results generated by the HG-focus platform. Secondarily, they were used to perform prediction analysis for disease severity. Samples were grouped into stages (G) based on the timepoint when they were collected: G0=day0 (on the day of fever onset); G1=day 1 (one day after fever onset); G2=day2 (two days after fever onset)M-bM-^@M-&until G5; G6=day6-10 (6-10 days after fever onset); G7= convalescent time point (around day 28 after the first sample). Samples were also grouped into early acute (G0-G3), late acute (G4-G6) and convalescent phases (G7). References for the protocols; PMID 12803996 and 20078211
2013-01-26 | E-GEOD-43777 | biostudies-arrayexpress
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:Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection The samples correspond to blood samples from 26 patients from a cohort in Brazil, divided into three classes, DHF, DF, ND, as follows: 18 were confirmed dengue 3, genotype III cases, among which 10 were diagnosed as dengue hemorrhagic fever (DHF) and 8 as classical dengue fever (DF), and 8 control samples (ND) from febrile patients confirmed to be not infected with dengue. None of the DHF patients presented vasculopathy signs and symptoms at the time the samples used in the functional genomic characterization were collected. At the time of collection the patients referred approximately 5 days of disease and the absence of fever was reported two to three days after enrollment. The samples from the DF, DHF and ND patients were matched to avoid significant differences regarding patient age, gender, dengue infection history and days of symptoms among the groups.
2010-09-01 | E-GEOD-18090 | biostudies-arrayexpress
Project description:In this study, we assessed the contribution of dengue-specific CD8+T cells in hospitalized samples with mild (dengue fever; DF) and severe (dengue hemorrhagic fever; DHF) forms of the disease. Our in-depth transcriptomic analysis provides no evidence for qualitative differences in terms of CD8+T cell response against dengue, therefore, concluding that CD8+T cell response is not a contributing factor in the development of severe dengue disease.
2021-09-21 | GSE174482 | GEO
Project description:We measured fever-day-specific genome-wide transcript abundance patterns in 105 peripheral blood mononuclear cell (PBMC) samples collected from 41 children hospitalized with dengue virus (DENV) infection in Nicaragua, and from 8 healthy controls. DF1 = primary DF; DF2 = secondary DF; DHF = Dengue Hemorrhagic Fever; DSS = Dengue Shock Syndrome. Samples were collected from pediatric patients with DENV infection at the Hospital Infantil Manuel de Jesus Rivera (HIMJR) in Managua, Nicaragua. Enrollment criteria consisted of hospitalized patients younger than 15 years of age whose parents or guardians completed the informed consent process, and for children 6 years and older who provided assent, and who presented with acute febrile illness of less than 7 days duration with one or more of the following symptoms or signs at the time of evaluation: headache, arthralgia, myalgia, retro-orbital pain, positive tourniquet test, petechiae, and signs of bleeding. Children were considered to have dengue if DENV was detected by RT-PCR or by isolation in cell culture, if an IgM ELISA indicated seroconversion between the acute and convalescent sample, and/or if there was a > 4-fold increase in DENV-specific antibodies between the acute and convalescent phase. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood within four hours of collection and stored in Trizol at -80 oC disease_state_design
2013-03-01 | E-GEOD-38246 | biostudies-arrayexpress
Project description:Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection
2010-09-01 | GSE18090 | GEO
Project description:Background: Dengue virus (DENV) infection often leads to acute illness lasting 2-7 days with severity ranging from dengue fever (DF) to hemorrhagic fever (DHF) and fatal dengue shock syndrome (DSS). The dynamic changes of host responses on the gene transcription level that accompany DENV infection and differences between DF and DHF cases have been poorly understood, particularly for South American population. Methodology/Principal Findings: Supported by a longitudinal active surveillance program for dengue transmission in Maracay, Venezuela, we conducted a prospective study to investigate host responses in dengue patients. Blood specimens and clinical information were collected on a daily basis from febrile cases confirmed with DENV infection from their first day of enrollment to early defervescence together with one convalescent sample. A total of 49 and 13 study participants were defined as DF and DHF cases respectively based on their clinical and hematological information. Using convalescent specimens as baseline, day-to-day gene expression was evaluated ex vivo in peripheral blood mononuclear cells of the study participants. Two waves of gene expression were detected: the first wave peaked at day 1 from the onset of fever (day 0) then declined at days 3-4; the second wave emerged from day 4 and peaked around day 5-6. Genes associated with innate immune process, including type I interferon signaling, cytokine-mediated signaling, chemotaxis, and antiviral responses, dominated the first wave; whereas genes involved in cell cycle processes, including cell division, mitosis, DNA replication, chromosome, and spindle organization dominated the second wave. Measureable genomic markers predicted early acute, late acute and convalescent phases with 91% accuracy. Gene signatures expressed in early acute phase predicted disease severity (DF vs DHF) with 96% accuracy. Conclusions/Significance: Our study established a dynamic pattern of detailed host immune responses to DENV infection and revealed genomic signatures valuable for diagnostics purposes.
2013-01-26 | GSE43777 | GEO
Project description:We investigated the abundances and transcriptomic changes of immune cells at several time points over the course of dengue virus infection. The PBMC samples were obtained from one dengue fever (DF) and one dengue hemorrhagic fever (DHF) patients (8 samples in total). The samples were harvested at two and one days before defervescence (febrile phase), at defervescence (critical phase), and two-week convalescence. Single-cell RNA-seq libraries were prepared using the 10x genomic protocol and were sequenced using the Illumina Hiseq platform. One healthy control sample analysed by the same protocol was included.
2022-02-16 | E-MTAB-9467 | biostudies-arrayexpress
Project description:We measured fever-day-specific genome-wide transcript abundance patterns in 105 peripheral blood mononuclear cell (PBMC) samples collected from 41 children hospitalized with dengue virus (DENV) infection in Nicaragua, and from 8 healthy controls. DF1 = primary DF; DF2 = secondary DF; DHF = Dengue Hemorrhagic Fever; DSS = Dengue Shock Syndrome. Samples were collected from pediatric patients with DENV infection at the Hospital Infantil Manuel de Jesus Rivera (HIMJR) in Managua, Nicaragua. Enrollment criteria consisted of hospitalized patients younger than 15 years of age whose parents or guardians completed the informed consent process, and for children 6 years and older who provided assent, and who presented with acute febrile illness of less than 7 days duration with one or more of the following symptoms or signs at the time of evaluation: headache, arthralgia, myalgia, retro-orbital pain, positive tourniquet test, petechiae, and signs of bleeding. Children were considered to have dengue if DENV was detected by RT-PCR or by isolation in cell culture, if an IgM ELISA indicated seroconversion between the acute and convalescent sample, and/or if there was a > 4-fold increase in DENV-specific antibodies between the acute and convalescent phase. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood within four hours of collection and stored in Trizol at -80 oC
2013-03-01 | GSE38246 | GEO
Project description:Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). While the mechanisms that lead to vascular permeability are unknown, the endothelium plays a central role in regulating fluid and cellular efflux from capillaries. Thus, dysregulation of endothelial cells functions by dengue virus infection may contribute to pathogenesis and severe disease. We used microarrays to investigate the effect of dengue virus infection on gene expression within primary human endothelial cells at various times post infection and identified numerous upregulated antiviral and immune response genes.
2012-04-11 | GSE34628 | GEO