Using transcriptomics to understand the compartment-specific effects of HIV on immune function in the lung and peripheral blood

Using transcriptomics to understand the compartment-specific effects of HIV on immune function in the lung and peripheral blood

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Human immune deficiency virus (HIV) remains a major health issue worldwide, and especially in sub-Saharan African. Mycobacterium Tubercolosis (MTB) co-infection has been reported to be the major cause of death in people living with HIV. Individuals with HIV are at high risk of developing lung infections in general, as most lung infections are opportunistic diseases. According to the World Organisation (WHO), about 90% of people maintain TB latent infection, with a lifetime risk of 10% of converting to active TB. But with HIV infection the 10% lifetime risk of converting to active TB is reduced to 10% annually. This is a serious concern and has raised many scientific questions of what is it that HIV does to the immune system, that facilitates the progression from latent to active TB infection.

HIV infection depletes CD4 helper T cells that play major role in protection against infections, and the cytotoxic CD8 T cells are expanded. This whole process is referred as chronic immune activation and this in turn leads to immune dysfunction. Most available information regarding immune system reaction towards HIV is extracted from the peripheral space and the impact of HIV in the lung space is poorly understood. Improved understanding of lung-specific immune alterations is a critical gap knowledge that has the potential to contribute to better ways of preventing and treating HIV-associated lung infections.

Whole blood transcriptomics is a new approach that provides a global view of the state of an individual's immune system. Recent studies have shown that whole blood transcriptomics can be used to identify individuals at risk for progression from latent TB to active TB. Therefore examining such signatures at the site of TB immune containment (the lung) could potentially lead to identification of novel biomarkers and the identification of relevant pathways for intervention.

Xulu’s study aims to estimate the prevalence of latent TB infection among the HIV-positive (ART-naïve) and HIV-negative individuals presenting for care in an already known peri-urban South African area for high prevalence of HIV and TB. Once all the latently infected people are identified, they will be recruited to provide blood and bronchoalveolar fluid thereby enabling performance of transcriptional analysis on these immune sites. The transcriptional data from the two sites is anticipated to provide information on the impact of HIV in the two compartments. Furthermore, still using transcriptomics analysis, Xulu will investigate the effect of HIV infection on specific immune cell types in the peripheral blood and bronchoalveolar lavage of people with LTBI (latent TB infection).