Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA308835 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Understanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases. We hypothesized that monocytes from household contacts of pulmonary tuberculosis patients that failed to convert their tuberculin skin tests (TSTNEG) would respond differently to M.tb infection when compared to matched tuberculin skin test positive controls (TSTPOS). We obtained genome-wide transcriptional profiles of M.tb-infected peripheral blood monocytes from 10 TSTNEG and 18 TSTPOS Ugandans. We used Gene Set Enrichment Analysis and interaction networks to identify cellular processes associated with TST status. We discovered gene sets associated with histone deacetylases that were differentially expressed when comparing TSTPOS and TSTNEG subjects. We used small molecule inhibitors to demonstrate that histone deacetylase function is important for the pro-inflammatory response to M.tb infection in monocytes. Monocytes from individuals who appear to resist M.tb infection differentially activate pathways controlled by histone deacetylase in response to M.tb infection when compared to those who are susceptible to infection. These data identify a potential cellular mechanism underlying the clinical phenomenon of persistently negative tuberculin skin tests despite known exposure to an infectious contact.
2016-01-15 | GSE76873 | GEO
Project description:Transcriptional profiling of biopsies from tuberculin skin test sites was performed to investigate the interaction of complex cellular and molecular networks at the interface between innate and adaptive immunity which coordinate anti-mycobacterial responses in vivo.
2012-05-13 | E-TABM-1157 | biostudies-arrayexpress
Project description:The overall scope of this study is to find early tuberculosis (TB) candidate protein biomarkers in different TB study groups vs. controls. The identified biomarkers may become the basis of a rapid diagnostic test able to identify active TB earlier than current practice. In addition, the candidate biomarkers may predict which patients are likely to convert from latent infection to active disease. . This project uses plasma and serum samples collected in a long-standing TB household contact study, the Kawempe Community Health Study, conducted in Kampala, Uganda, a TB endemic area. The study utilizes samples from TB index cases and household contacts that were negative for TB at recruitment. A subset of these contacts developed Mtb infection (i.e., their Tuberculin Skin Test (TST) converted to positive) after 3-6 months, and smaller subset developed active TB after 3 months of follow-up. Control patients were still TST negative at 12 months or 24 months of follow-up. This dataset corresponds to the discovery phase of the study.
2019-11-25 | PXD000582 | Pride
Project description:Understanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases. We hypothesized that monocytes from household contacts of pulmonary tuberculosis patients that failed to convert their tuberculin skin tests (TSTNEG) would respond differently to M.tb infection when compared to matched tuberculin skin test positive controls (TSTPOS). We obtained genome-wide transcriptional profiles of M.tb-infected peripheral blood monocytes from 10 TSTNEG and 18 TSTPOS Ugandans. We used Gene Set Enrichment Analysis and interaction networks to identify cellular processes associated with TST status. We discovered gene sets associated with histone deacetylases that were differentially expressed when comparing TSTPOS and TSTNEG subjects. We used small molecule inhibitors to demonstrate that histone deacetylase function is important for the pro-inflammatory response to M.tb infection in monocytes. Monocytes from individuals who appear to resist M.tb infection differentially activate pathways controlled by histone deacetylase in response to M.tb infection when compared to those who are susceptible to infection. These data identify a potential cellular mechanism underlying the clinical phenomenon of persistently negative tuberculin skin tests despite known exposure to an infectious contact. CD14+ monocytes from 18 TSTPOS and 10 TSTNEG subjects were isolated by positive selection. Depending on the yield, between 5E5 and 1E6 monocytes were plated in duplicate in a 24-well tissue culture plate and rested overnight at 37oC, 5% CO2. The next day, cells were mock-infected or infected with virulent M. tuberculosis strain H37Rv at a multiplicity of infection (MOI) 10:1. After a six hour incubation at 37C, 5% CO2, the mycobacteria were killed and total RNA harvested using TRIzol-LS (Invitrogen). TRIzol samples were stored at -80oC until all infections were completed. To minimize batch effects, equal numbers of TSTPOS and TSTNEG subjects were processed on each of six days and frozen aliquots of M.tb were used for infections. RNA was extracted using the RNeasy Mini Kit with on-column DNAse digestion. RNA was transcribed into complementary DNA, labeled, and hybridized onto Illumina HT-12 microarrays according to the manufacturerâs instructions. Probe intensities were quantified using Illumina iScan platform and processed using BeadArray without performing normalization or background correction.
2016-01-15 | E-GEOD-76873 | biostudies-arrayexpress
Project description:Transcriptional profiling of the tuberculin skin test in patients with active and latent tuberculosis
| PRJEB56765 | ENA
Project description:Transcriptome at the site of a 48 hour tuberculin skin test (TST) and saline injection from patients with active TB disease and latent TB infection
2019-05-01 | E-MTAB-6816 | biostudies-arrayexpress
Project description:Transcriptional profiling of the tuberculin skin test in individuals cured of active tuberculosis disease (RNA-Seq)
| PRJEB33786 | ENA
Project description:Validation of gene expression levels to assess classification of TB patients and healthy controls qPCR gene expression profiling. Whole blood gene expression from TB patients (positive in GenXpert assay) and healthy controls; both tuberculin skin test positive (TSTpos) and -negative (TSTneg).
2015-12-21 | E-GEOD-74092 | biostudies-arrayexpress
Project description:Transcriptional profiling of the tuberculin skin test in individuals cured of active tuberculosis disease (RNA-Seq)
2025-01-16 | E-MTAB-8163 | ExpressionAtlas
Project description:Anti-TNF therapy has transformed the management of rheumatoid arthritis (RA); however little is known about its effects on cell mediated immune responses and TNF-inducible activity at the site of inflammation. Here, we used the tuberculin skin test (TST) as a standardised in vivo human challenge model to make systems level assessments of the effects of anti-TNF therapy in a prototypic cell mediated immune response. RA patients (treated with monoclonal anti-TNF antibodies (adalimumab or infliximab), the soluble TNF receptor etanercept or the standard therapy methotrexate) and healthy volunteers with immunological memory to Mycobacterium tuberculosis antigens were identified using an interferon-γ release assay of peripheral blood. Two units tuberculin or an equivalent volume of saline was injected into the forearm of study participants (n=50). After 72 hours, 3 mm skin punch biopsies were taken from the injection site and processed for whole genome transcriptional profiling by Agilent gene microarray.
2017-08-04 | E-MTAB-5093 | biostudies-arrayexpress