Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic impairment and blunted transcriptional response to Mycobacterium tuberculosis of alveolar macrophages from persons living with HIV (ATAC-Seq)

ABSTRACT: Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is mainly the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. In this study AM were challenged in vitro with Mtb, and their epigenetic and transcriptomic responses were determined for PLWH receiving ART, control subjects who were HIV-free (HC) and subjects who received pre-exposure prophylaxis (PrEP) with ART to prevent HIV infection. Compared to HC subjects’ response to Mtb, we showed that AM isolated from PLWH and PrEP subjects displayed substantially weaker transcriptomic response and no significant changes in their chromatin state. These findings revealed a previously unknown adverse effect of ART.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165703 | GEO | 2021/09/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic impairment and blunted transcriptional response to Mycobacterium tuberculosis of alveolar macrophages from persons living with HIV (RNA-Seq)

Project description:Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is mainly the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. In this study AM were challenged in vitro with Mtb, and their epigenetic and transcriptomic responses were determined for PLWH receiving ART, control subjects who were HIV-free (HC) and subjects who received pre-exposure prophylaxis (PrEP) with ART to prevent HIV infection. Compared to HC subjects’ response to Mtb, we showed that AM isolated from PLWH and PrEP subjects displayed substantially weaker transcriptomic response and no significant changes in their chromatin state. These findings revealed a previously unknown adverse effect of ART.

2021-09-03 | GSE165708 | GEO

Epigenetic impairment and blunted transcriptional response to Mycobacterium tuberculosis of alveolar macrophages from persons living with HIV (ChIP-Seq)

2021-09-03 | GSE165705 | GEO

INTEGRATIVE MULTI-OMICS REVEAL A TWO-ANALYTE BLOOD-BASED SIGNATURE FOR TB DIAGNOSIS IN ADVANCED HIV

Project description:Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to diagnose subclinical and difficult to diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating ART with CD4 cell counts <50 cells/uL. Twenty-three cases of incident TB were site-matched with 32 controls to identify miRNAs, cytokines/chemokines, and metabolites associated with the development of newly diagnosed TB in PLWH. Differentially expressed miRNA analysis revealed 11 altered miRNAs with a fold change higher than ±1.4 in cases relative to controls (p<0.05). Differentially altered metabolite analysis showed no significant alterations in metabolites between cases and controls. We found higher TNFα and IP-10/CXCL10 in cases (p=0.011, p=0.0005), and higher MDC/CCL22 in controls (p=0.0072). A decision tree algorithm identified gamma-glutamylthreonine and hsa-miR-215-5p as the optimal variables to classify incident TB cases (AUC 0.965). hsa-miR-215-5p, which targets genes in the TGF-β signaling pathway, was downregulated in cases. Gamma-glutamylthreonine, a breakdown product of protein catabolism, was less abundant in cases. To our knowledge, this is one of the first uses of a multi-omics approach to identify incident TB in a severely immunosuppressed PLWH study.

2021-06-30 | GSE166557 | GEO

Discovery of serum protein biomarkers of Active Tuberculosis in HIV- and HIV+ Individuals (US center)

Project description:The overall goal of the project is to identify candidate biomarkers of Active infection with Mycobacterium tuberculosis (Mtb) in individuals with or without HIV. Samples were analyzed from two tuberculosis (TB) endemic countries, Brazil and South Africa (SA), as well as from the United States (US). The US site included patients that were in the early stages of Active TB, with mean symptom duration of 1.5 months. The subjects from the Brazil site had mean symptom duration of 6 months, and the SA site subjects had advanced TB. All sites also provided samples asymptomatic for TB or with Latent TB infection. The US and SA sites also had subjects with and without HIV co-infection, whereas the Brazilian subjects were all HIV-. This specific dataset corresponds to the Discovery step of the study, for the US center.

2019-11-22 | PXD000517 | Pride

Innate and antigen-specific cytotoxic cells and Paradoxical HIV-associated Tuberculosis Immune reconstitution inflammatory syndrome (TB-IRIS)

Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray Blood samples were collected during longitudinal observational studies of TB-IRIS patients and controls (both groups HIV-infected patients placed on antiretroviral treatment). PBMC were stimulated with heat killed H37Rv and RNA extracted.

2013-06-24 | E-GEOD-48237 | biostudies-arrayexpress

The immunosuppressive Tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4+ T cells

Project description:Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the most common coinfection among people living with HIV-1. This coinfection alters the efficacy of the immune response against both HIV-1 and Mtb, and is associated with accelerated HIV-1 disease progression and reduced survival. Enhanced HIV-1 replication in macrophages induced by Mtb coinfection may contribute to the worsened clinical outcomes observed in HIV-1/TB coinfected individuals. However, the impact of the HIV-1/TB coinfection on HIV-1 replication and latency in CD4+ T cells remains poorly studied. In this study, we used the acellular fraction of tuberculous pleural effusion (TB-PE) as a proxy for the microenvironment generated by Mtb infection. Using this physiologically relevant fluid, we investigated whether viral replication and HIV-1 latency in CD4+ T cells are affected by a TB-associated microenvironment. Interestingly, our results revealed that TB-PE shaped the transcriptional profile of CD4+ T cells impairing T cell receptor-dependent cell activation and decreased HIV-1 replication. Moreover, this immunosuppressive TB microenvironment promoted viral latency and inhibited HIV-1 reactivation in CD4+ T cells from people living with HIV-1. This study indicates that the immune response induced by TB may contribute to the persistence of the viral reservoir by silencing HIV-1 expression in individuals coinfected with both pathogens, allowing the virus to persist undetected by the immune system and increasing the size of the HIV-1 latent reservoir in cells at the site of the coinfection.

2024-07-01 | GSE248986 | GEO

Innate and antigen-specific cytotoxic cells and Paradoxical HIV-associated Tuberculosis Immune reconstitution inflammatory syndrome (TB-IRIS)

2013-06-24 | GSE48237 | GEO

A two-gene signature for diagnosis of tuberculosis in persons with advanced HIV

Project description:Background: Tuberculosis (TB) among persons living with HIV (PLWH) poses diagnostic challenges. Although several transcriptional signatures have recently been identified as promising tool for TB diagnosis, data are limited in persons with advanced HIV. Methodology: Reads were aligned to the human transcriptome (GRCh38 version 100), comprising both mRNA and ncRNA, with Salmon v1.2.0. A Random Forest algorithm with “leave-one-out” cross-validation was applied in the variance stabilizing transformation gene expression. The identified biomarkers were compared to previous TB transcriptional signatures using the Area Under the Curve (AUC). Results: Functional analysis indicated that common upregulated pathways in TB/HIV patients were associated with Toll-like receptor cascades and neutrophil degranulation. A machine learning decision tree algorithm identified the expression values from RAB20 and INSL3 as most informative for classifying TB status in PLWH. Only these two genes were able to correctly classify all samples.

2021-02-02 | GSE162164 | GEO

Trans cohorts metabolic reprograming towards glutaminolysis in long-term successfully treated HIV-Infection: potential role in accelerated aging and latency reversal

Project description:Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon and India, respectively to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids were observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.

2021-11-24 | PXD028531 | Pride

Antiretroviral treatment induced decrease in immune activation contributes to reduced susceptibility to tuberculosis in HIV-TB co-infected persons

Project description:Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV co-infected persons. We aimed to investigate the mechanisms of ART-mediated prevention of TB in HIV and TB co-infected patients on antiretroviral therapy (ART), recruited in Khayelitsha, South Africa. RNA was extracted from whole blood collected in TempusTM Blood RNA tubes at day 0 and at 1, 3 and 6 months of ART. We first performed a pilot RNAseq experiment of 12 samples (3 patients at 4 timepoints) for 50 million reads to assess if samples with lower quality and/or quantity will still yield meaningful outputs and the minimum number of reads required for sufficient coverage. This was followed by a second RNAseq experiment of 35 samples with sufficient quality: 11 from day 0 and 24 from 6 months of ART, 8 of which are paired. However, only n=6 samples from day 0 and n=6 samples from 6 months of ART could be analyzed. Results indicated reduced immune activation at 6 months of ART compared to day 0 with significant fall in the Hallmark Interferon alpha, Interferon gamma and IL-6-JAK-STAT-signalling pathway genes. These results were supported by similar changes in soluble protein markers in the plasma. Overall, our data indicates that ART- induced decrease in immune activation may contribute to reduced susceptibility to tuberculosis in HIV-TB co-infected persons.

2021-02-17 | GSE158208 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data