Increased plasmacytoid dendritic cells and inflammation persist in people with HIV years after tuberculosis.

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.