Persistent Increased Plasmacytoid Dendritic Cells and Inflammation in People With HIV Years After Tuberculosis.

BACKGROUND: People living with human immunodeficiency virus (HIV-1) who have a history of cured tuberculosis have worse outcomes, including increased all-cause mortality rate and risk of recurrent tuberculosis. We hypothesized that persistent and global immune deficits could contribute to these outcomes in people with a history of tuberculosis.

METHODS: We completed FLEX Cellular Indexing of Transcriptomes and Epitopes by Sequencing (FLEX-CITE-Seq) of peripheral blood mononuclear cells of people living with HIV with (n = 6) or without (n = 3) a history of tuberculosis 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 significantly differential levels of expression for >40 genes all had overrepresentation of a tumor necrosis factor (TNF)-mediated pathway. In an expanded cohort of 29 people living with HIV, we found a larger percentage of plasmacytoid dendritic cells by flow cytometry and increased plasma interleukin 6, 12p70, 15, and 2, interferon α, and TNF levels in the tuberculosis history group (n = 18) than in the group with no history of tuberculosis (n = 11).

CONCLUSIONS: A proinflammatory milieu and immune cell gene expression changes mediated by TNF persist in people living with HIV even years after tuberculosis is cured. It remains to be determined whether the differences are preexisting risk factors or are established during the natural history of HIV and tuberculosis infections.