Gene expression of neutrophils in response to Mtb infection in persons living with HIV
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PROVIDER: EGAS00001007262 | EGA |
REPOSITORIES: EGA
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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 | GSE165703 | GEO
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
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 | GSE165705 | GEO
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
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
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
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
Project description:Mycobacterium tuberculosis (M. tb), the cause of tuberculosis (TB), utilizes the blood circulation to spread systemically and establish infection, and the risk of developing active TB (pulmonary and extrapulmonary) is significantly increased in individuals infected with human immunodeficiency virus (HIV). In this work, we have used DNA microarray analysis to investigate the transcriptome of M. tb replicating in human whole blood from both HIV-negative and HIV-positive donors compared to M. tb grown in Middlebrook 7H9 broth media in order to identify M. tb adaptations to this host environment as well as M. tb mechanisms/factors contributing to increased active and disseminated TB during M. tb/HIV co-infection. We compared the global gene expression of M. tb H37Rv replicating in whole blood from 6 HIV- and 6 HIV+ individulas at 96 hr to M. tb grown to log phase in Middlebrook 7H9 media.
2014-03-31 | E-GEOD-49760 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis (M. tb), the cause of tuberculosis (TB), utilizes the blood circulation to spread systemically and establish infection, and the risk of developing active TB (pulmonary and extrapulmonary) is significantly increased in individuals infected with human immunodeficiency virus (HIV). In this work, we have used DNA microarray analysis to investigate the transcriptome of M. tb replicating in human whole blood from both HIV-negative and HIV-positive donors compared to M. tb grown in Middlebrook 7H9 broth media in order to identify M. tb adaptations to this host environment as well as M. tb mechanisms/factors contributing to increased active and disseminated TB during M. tb/HIV co-infection.
2014-03-31 | GSE49760 | GEO
Project description:Genome wide DNA methylation profiling of PBMC from South African patients either infected with HIV only or coinfected with HIV and tuberculosis (TB). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles from PBMC samples. Samples included 19 HIV patients and 20 HIV/TB co-infected patients.
2014-03-05 | GSE50835 | GEO