📖 ABSTRACT/OVERVIEW
HIV-TB co-infection represents the most challenging dual infectious burden globally, yet the single-cell immunological landscape of co-infected patients receiving simultaneous antiretroviral and anti-tuberculous therapy in African populations remains completely uncharacterised. This research applies single-cell RNA sequencing to dissect the transcriptional heterogeneity of peripheral blood mononuclear cells in HIV-TB co-infected patients in Kano State, North West Nigeria. A cross-sectional design will recruit 30 HIV-TB co-infected patients, 30 HIV mono-infected, 30 TB mono-infected, and 30 healthy controls at Aminu Kano Teaching Hospital. PBMCs will be isolated by density gradient centrifugation and subjected to 10x Genomics Chromium single-cell RNA-seq, targeting 5,000 cells per participant. Seurat-based clustering, trajectory analysis, and intercellular communication inference using CellChat will characterise cell type proportions, transcriptional states, and signalling networks. Regulatory T cell and macrophage polarisation states will receive particular focus given their central roles in both TB immune suppression and HIV-driven CD4 depletion. Pseudotime analysis will model PBMC state transitions during dual therapy. Original contributions include the first single-cell immunological atlas of HIV-TB co-infection in a Nigerian population, discovery of previously undefined co-infection-specific immune cell states, and identification of molecular targets for immunomodulatory interventions. The theoretical framework proposes a co-infection immune dysregulation model integrating mycobacterial and retroviral immunopathology for West African populations. Keywords: single-cell RNA sequencing, HIV-TB co-infection, PBMCs, immunological atlas, Kano State
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