Characterization of Distinct Monocyte Subtypes and Immune Features Associated with HIV, Tuberculosis, and Coronary Artery Disease in a Ugandan Cohort Using Mass Cytometry

Coronary artery disease (CAD), tuberculosis (TB), and HIV represent major global health burdens. Individuals affected by one or more of these conditions often exhibit chronic inflammation and immune dysregulation, with monocytes playing a central role in these processes. Monocyte subsets are known to expand in individuals with HIV, TB, or CAD. However, the precise mechanisms by which these cells contribute to inflammation and immune responses in the context of these conditions remain poorly understood. In this study, we employed high-dimensional mass cytometry to characterize monocyte heterogeneity in 61 Ugandan adults with varying combinations of HIV, latent TB, and subclinical or overt CAD. Through an integrative approach combining manual gating, unsupervised clustering, and elastic net penalization, we identified distinct monocyte phenotypes associated with CAD and TB. Importantly, individuals with CAD, especially those with more extensive disease (Segment Involvement Score >2), showed reduced surface expression of the anti-inflammatory scavenger receptor CD163 on non-classical monocytes. Notably, unsupervised clustering further revealed two distinct non-classical monocyte subsets associated with disease states: A CD86 ^dim CX3CR1 ^dim CD45RA ⁺ GPR56 ⁺ CXCR3 ⁺ subset significantly depleted in individuals with CAD, and a CD86 ⁺ CX3CR1 ⁺⁺ CD45RA ⁺⁺ GPR56 ⁻ CD38 ⁻ CXCR3 ⁻ subset enriched in individuals with TB. These findings underscore the complexity of the monocyte landscape in CAD progression, particularly within settings of HIV and TB co-endemicity. We hope this work motivates further research and offers insights for the development of new precision biomarkers and immune-targeted therapies to prevent or treat CAD, TB, and HIV in populations.