Increased plasmacytoid dendritic cells and inflammation persist in people with HIV years after tuberculosis.
Academic Article
Overview
abstract
BACKGROUND: People living with HIV who have history of cured TB have worse outcomes, including increased all-cause mortality and risk for recurrent TB. We hypothesized that persistent and global immune deficits could contribute to these outcomes in people with history of TB. METHODS: We completed FLEX Cellular Indexing of Transcriptomes and Epitopes by Sequencing of PBMC of people living with HIV with (n=6) or without (n=3) TB history at GHESKIO Centers in Haiti. We subtyped dendritic cells using flow cytometry and quantitated cytokines on an expanded cohort (n=29) to confirm FLEX-CITE-Seq findings. RESULTS: Cell types with statistically significantly differential levels of expression for more than 40 genes all had over-representation of a TNF-mediated pathway. In an expanded cohort of 29 people with HIV, we found a larger percentage of plasmacytoid dendritic cells by flow cytometry and increased plasma IL-6, IL-12p70, IL-15, IL-2, IFN-alpha, and TNF in the TB history group (n=18) compared to people with no history of TB (n=11). DISCUSSION: A proinflammatory milieu and immune cell gene expression changes mediated by TNF persist in people living with HIV even years after TB cure. If the differences are pre-existing risk factors or establish during the natural history of HIV and TB infections is still to be determined.
