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

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

PROVIDER: PRJNA664368 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12670006_1.fastq.gz	Fastqsanger.gz
	SRR12670006_2.fastq.gz	Fastqsanger.gz
	SRR12670007_1.fastq.gz	Fastqsanger.gz
	SRR12670007_2.fastq.gz	Fastqsanger.gz
	SRR12670008_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons.

Project description:Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV-1 co-infected persons. In order to understand host immune responses during ART in the context of Mycobacterium tuberculosis (Mtb) sensitization, we performed RNAseq analysis of whole blood-derived RNA from individuals with latent TB infection coinfected with HIV-1, during the first 6 months of ART. A significant fall in RNA sequence abundance of the Hallmark IFN-alpha, IFN-gamma, IL-6/JAK/STAT3 signaling, and inflammatory response pathway genes indicated reduced immune activation and inflammation at 6 months of ART compared to day 0. Further exploratory evaluation of 65 soluble analytes in plasma confirmed the significant decrease of inflammatory markers after 6 months of ART. Next, we evaluated 30 soluble analytes in QuantiFERON Gold in-tube (QFT) samples from the Ag stimulated and Nil tubes, during the first 6 months of ART in 30 patients. There was a significant decrease in IL-1alpha and IL-1beta (Ag-Nil) concentrations as well as MCP-1 (Nil), supporting decreased immune activation and inflammation. At the same time, IP-10 (Ag-nil) concentrations significantly increased, together with chemokine receptor-expressing CD4 T cell numbers. Our data indicate that ART-induced decrease in immune activation combined with improved antigen responsiveness may contribute to reduced susceptibility to tuberculosis in HIV-1/Mtb co-infected persons.

| S-EPMC7973093 | biostudies-literature

Changes in bacterial diversity and composition detected in plasma determine immunological outcome in HIV+ persons initiating antiretroviral therapy

Project description:Changes in bacterial diversity and composition detected in plasma determine immunological outcome in HIV+ persons initiating antiretroviral therapy

| PRJNA727238 | ENA

Single-cell analysis of adipose tissue T cells in diabetic persons with HIV reveals high proportions of clonally expanded CMV-like CD4+ T cells with cytotoxic RNA transcriptomes

Project description:Persons with HIV have a disproportionate burden of metabolic disease, including type 2 diabetes. We hypothesized that the accumulation of chronically activated T cells in the adipose tissue of HIV+ persons is a central mechanism promoting local macrophage activation, impaired adipocyte function, and the development of HIV-associated glucose intolerance. Prior studies of immune activation and HIV-associated metabolic disease have only measured circulating T cell subsets. In contrast, in our study we recruited a longitudinal cohort of HIV+ patients on antiretroviral therapy ranging from insulin sensitive to overtly diabetic, in addition to HIV-negative diabetic controls, to identify potential mechanistic linkages between adipose-resident T cell cytokine signaling, adipose tissue inflammation, and glucose intolerance in HIV+ persons. This study may also provide further insight into the role of T cells in the development of glucose intolerance in HIV-negative patients.

2020-10-22 | GSE159759 | GEO

Transcription profiling of CD8 T cell subsets from healthy young and elderly persons

Project description:We isolated highly purified CD8+CD28+ and CD8+CD28- T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28- T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8?CD28- (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28- T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types.

2010-09-03 | E-MEXP-2345 | biostudies-arrayexpress

DNA methylation data for older persons with vs. without mild cognitive impairment

Project description:Genome wide DNA methylation assays was conducted using the Illumina Infinium MethylationEPIC BeadArray technology (Methyl850K chip) that allows genome-wide DNA methylation analysis of 866,836 CpG sites. We included baseline and 2-year follow-up samples from 25 persons with mild cognitive impairment (cases) and 20 persons with cognitively normal (controls). Sample was balanced by age and sex.

2021-12-10 | GSE190540 | GEO

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

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

2021-09-03 | GSE165703 | GEO

Long-term Antiretroviral Treatment Initiated in Primary HIV-1 Infection Affects the Size, Composition and Decay Kinetics of the Reservoir of HIV-1 Infected CD4 T Cells

Project description:Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy in primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of therapy in chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed exclusively during the initial 3-4 years of treatment; however, in patients who started antiretroviral therapy in acute infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. Moreover, gene transcripts in CD4 T cells associated with the total viral CD4 T cell reservoir size frequently correlated with the relative proportion of these long-lived CD4 T cell subsets, suggesting shared gene expression signatures for maintaining HIV-1 persistence and preservation of long-lasting CD4 T cell subsets. Despite effective suppression of viral antigens for >10 years, HIV-1-specific T cell responses remained continuously detectable in both study groups. Together, these data suggest that although early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients attractive candidates for future interventional studies aiming at HIV-1 eradication and cure.

2017-01-01 | GSE53527 | GEO

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