Orientsia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Thanavadee Prachason
PROVIDER: E-GEOD-16463 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Comparative analysis of Genome wide expression was performed to demonstrate diagnostic potential of expression profiling and to identify host response genes in scrub typhus. The results showed that there is a unique expression pattern in peripheral blood leukocytes of scrub typhus infected patients that could discriminate scrub typhus from the other infections and also provided insight into host transcriptional responses to this paticular infection.
2011-03-26 | GSE16463 | GEO
Project description:Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus. As O. tsutsugamushi is detected in circulating monocytes during acute phase of scrub typhus, we wondered if this organism was able to infect monocytes. We showed here that O. tsutsugamushi replicated in monocytes from healthy donors. Using human whole genome microarrays, we found that O. tsutsugamushi the expression of genes in which up-regulated and down-modulated genes were equally distributed. , the expression of type I interferon, interferon-stimulated genes and M1-associated genes was significantly up-regulated. Second, O. tsutsugamushi the expression of apoptosis-related genes and induced cell death in monocytes. Live organisms were indispensable to type I interferon response and apoptosis and enhanced the expression of M1 cytokines. These findings were related to the transcriptional changes found in mononuclear cells from patients with scrub typhus. Hence, a microarray study revealed the up-regulation of 613 genes and the down-modulation of 517 genes. Importantly, IFN-related genes were specifically enriched and some features of M1 polarization were observed in patients, as found in O. tsutsugamushi-stimulated cells. Our results provide a comprehensive understanding of scrub typhus pathogenesis in which IFN-mediated activation of monocytes appears as critical.
2010-09-21 | GSE24247 | GEO
Project description:Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus. As O. tsutsugamushi is detected in circulating monocytes during acute phase of scrub typhus, we wondered if this organism was able to infect monocytes. We showed here that O. tsutsugamushi replicated in monocytes from healthy donors. Using human whole genome microarrays, we found that O. tsutsugamushi the expression of genes in which up-regulated and down-modulated genes were equally distributed. , the expression of type I interferon, interferon-stimulated genes and M1-associated genes was significantly up-regulated. Second, O. tsutsugamushi the expression of apoptosis-related genes and induced cell death in monocytes. Live organisms were indispensable to type I interferon response and apoptosis and enhanced the expression of M1 cytokines. These findings were related to the transcriptional changes found in mononuclear cells from patients with scrub typhus. Hence, a microarray study revealed the up-regulation of 613 genes and the down-modulation of 517 genes. Importantly, IFN-related genes were specifically enriched and some features of M1 polarization were observed in patients, as found in O. tsutsugamushi-stimulated cells. Our results provide a comprehensive understanding of scrub typhus pathogenesis in which IFN-mediated activation of monocytes appears as critical. Monocytes (1.5 x 105 per assay) were incubated with or without 3 x 105 O. tsutsugamushi organisms in RPMI 1640 containing 10% FBS, 20 mM HEPES and 2 mM L-glutamine (Invitrogen) for 2 hours. The raw data, from the Agilent feature extraction software, were preprocessed with background subtraction and quantile normalization. This pretreatment was performed by using a bioconductor limma package, called Agi4x44PreProcess (http://www.bioconductor.org/packages/2.3/bioc/html/ Agi4x44PreProcess.html)
2010-09-21 | E-GEOD-24247 | biostudies-arrayexpress
Project description:Infection with dengue viruses (DENVs) leads to a spectrum of disease outcomes. The pathophysiology of severe versus non-severe manifestations of DENV infection may be driven by host responses, which could be reflected in the transcriptional profiles of peripheral blood immune cells. We conducted genome-wide microarray analysis of whole blood RNA from 34 DENV-infected children in Nicaragua collected on days 3–6 of illness, with different disease manifestations. Gene expression analysis identified genes that are differentially regulated between clinical subgroups. The most striking transcriptional differences were observed between dengue patients with and without shock, especially in the expression of mitochondrial ribosomal proteins associated with protein biosynthesis. In the dengue hemorrhagic fever patients, one subset of differentially expressed genes encode neutrophil-derived anti-microbial peptides associated with innate immunity. We analyzed 44 HEEBO arrays on which were hybridized RNA amplified from whole blood collected into PAXgene tubes. 34 samples were collected from DENV-infected patients who presented between days 3-6 of illness. Six convalescent samples collected 14-19 days after onset of symptoms were from two dengue fever patients, one dengue hemorrhagic fever patient and three dengue shock syndrome patients. Additionally, samples from four normal healthy individuals were also analyzed.
2010-11-20 | E-GEOD-25226 | biostudies-arrayexpress
Project description:Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflict ~50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue largely remain unnoticed. The immune correlates conferring protection to individuals that remain clinically asymptomatic have seldom been investigated. We determined the gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms and signs consistent to clinical dengue infection. Results provide insight in association of certain host genes to protection against clinical dengue. Blood samples were collected from Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF) patients in Malaysia who were admitted to university of Malaya Medical Centre (UMMC), Ampang Hospital (AmpangHospital), and Hospital Tengku Ampuan Rahimah (HTAR) Klang. Blood from their asymptomatic household members were also collected. Their peripheral blood mononuclear cells (PBMCs) were isolated. 29 sample pairs (SP) of dengue patients and their accompanying asymptomatic household members were chosen on the following basis for two-channel microarray experiments: patients who have shown positive results for DENV infection with at least 2 diagnostics tests indicating positivity. Positive results for the IgM-captured ELISA were P/N ratio more than 2.0, while total antibody titer of more than 1:2560 or 4 fold increase from acute to convalescence phase was considered positive in HI assay. PRNT, a neutralization test, was used as a measure for levels of neutralizing antibodies and was considered high when it was more than 1:640, based on a reduction neutralization of 50%.
2013-09-06 | E-GEOD-50634 | biostudies-arrayexpress
Project description:DNA microarrays and specific RT-PCR assays were used to reveal transcriptional patterns in the blood of children presenting with dengue shock syndrome (DSS) and well-matched patients with uncomplicated dengue. The transcriptome of patients with acute uncomplicated dengue was characterized by a metabolically demanding "host defense" profile; transcripts related to oxidative metabolism, interferon signaling, protein ubiquination, apoptosis and cytokines were prominent. In contrast, the transcriptome of DSS patients was surprisingly benign, particularly with regard to transcripts derived from apoptotic and type I interferon pathways. These data highlight significant heterogeneity in the type or timing of host transcriptional immune responses precipitated by DENV infection independent of the duration of illness. In particular, they suggest that if transcriptional events in the blood compartment contribute to capillary leakage leading to hypovolemic shock, they occur before cardiovascular decompensation occurs, a finding that has implications for rational adjuvant therapy in this syndrome. Whole blood transcriptional profiles of children infected with dengue virus with different clinical outcomes were compared. The subjects including 9 acute dengue shock samples, 9 acute uncomplicated dengue samples, 6 autologous follow up dengue samples and 6 autologous follow up uncomplicated dengue patients. Microarray data was normalised using Genespring GX7 software, statistical analysis was performed in Multiexperiment viewer software. Pathway analysis was performed using Ingenuity Pathway analysis online software.
2008-12-18 | E-GEOD-13052 | biostudies-arrayexpress
Project description:Infection with dengue viruses (DENVs) leads to a spectrum of disease outcomes. The pathophysiology of severe versus non-severe manifestations of DENV infection may be driven by host responses, which could be reflected in the transcriptional profiles of peripheral blood immune cells. We conducted genome-wide microarray analysis of whole blood RNA from 34 DENV-infected children in Nicaragua collected on days 3–6 of illness, with different disease manifestations. Gene expression analysis identified genes that are differentially regulated between clinical subgroups. The most striking transcriptional differences were observed between dengue patients with and without shock, especially in the expression of mitochondrial ribosomal proteins associated with protein biosynthesis. In the dengue hemorrhagic fever patients, one subset of differentially expressed genes encode neutrophil-derived anti-microbial peptides associated with innate immunity.
2010-11-20 | GSE25226 | 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: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
Project description:This pilot study, aimed to profile the host transcriptome as a potential strategy for identifying specific biomarkers for dengue prediction and detection. High-throughput RNA-sequencing (RNA-seq) was employed to generate host transcriptome profiles in 16 dengue patients and 10 healthy controls. Differentially expressed genes (DEGs) were identified in patients with severe dengue and those with dengue with warning signs compared to healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of upregulated and downregulated genes. Compared to healthy controls, 6466 genes were significantly differentially expressed (P < 0.05) in the dengue with warning signs group and 3082 genes in the severe dengue group, with over half being upregulated. The major KEGG pathways implicated included transport and catabolism (14.4%-16.3%), signal transduction (6.6%-7.3%), global and overview maps (6.7%-7.1%), viral diseases (4.6%-4.8%), and the immune system (4.4%-4.6%). Several genes exhibited consistent and significant upregulation across all dengue patients, regardless of severity: Interferon alpha inducible protein 27 (IFI27), Potassium Channel Tetramerisation Domain Containing 14 (KCTD14), Syndecan 1 (SDC1), DCC netrin 1 receptor (DCC), Ubiquitin C-terminal hydrolase L1 (UCHL1), Marginal zone B and B1 cell specific protein (MZB1), Nestin (NES), C-C motif chemokine ligand 2 (CCL2), TNF receptor superfamily member 17 (TNFSF17), and TNF receptor superfamily member 13B (TNFRSF13B). Further analysis revealed potential biomarkers for severe dengue prediction, including TNF superfamily member 15 (TNFSF15), Plasminogen Activator Inhibitor-2 (SERPINB2), motif chemokine ligand 7 (CCL7), aconitate decarboxylase 1 (ACOD1), Metallothionein 1G (MT1G) and Myosin Light Chain Kinase (MYLK2), which were expressed 3.5 times, 2.9 times, 2.3 times, 2.1 times, 1.7 times, and 1.4 times greater, respectively, than dengue patients exhibiting warning signs. The identification of these host biomarkers through RNA-sequencing holds promising implications and potential to augment existing dengue detection algorithms, contributing significantly to improved diagnostic and prognostic capabilities.
2024-10-10 | GSE279208 | GEO