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| Status |
Public on Jul 01, 2024 |
| Title |
The immunosuppressive Tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4+ T cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
To understand the effect of the immune response to TB on CD4+ T cells and its potential impact on HIV-1 replication, we assessed the transcriptional profile of primary CD4+ T cells treated with TB-PE. Bulk RNA sequencing (RNAseq) was performed on primary CD4+ T cells isolated from 3 healthy donors and treated with TB-PE. In addition, since T cell activation increases CD4+ T cells susceptibility to HIV-1 infection, we also investigated the impact of TB-PE on CD4 T cells activated by anti-CD3/CD28 antibodies.
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| Contributor(s) |
Duette G, Lai J, Gloss B, Cronin S, Palmer S |
| Citation(s) |
39055929 |
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| Submission date |
Nov 29, 2023 |
| Last update date |
Aug 16, 2024 |
| Contact name |
Gabriel Duette |
| E-mail(s) |
gabriel.duette@gmail.com
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| Phone |
+61286273630
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| Organization name |
The Westmead Institute for Medical Research
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| Department |
Centre for Virus Research
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| Lab |
Palmer's lab
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| Street address |
176 Hawkesbury Road
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| City |
Westmead |
| State/province |
NSW |
| ZIP/Postal code |
2145 |
| Country |
Australia |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1046537 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248986_RAW.tar |
3.8 Mb |
(http)(custom) |
TAR (of TAB) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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