Single-cell sequencing reveals the heterogeneity of immune landscape in drug users with HIV infection

Abstract

Background

Injection drug use (IDU) leads to immune system dysfunction, thereby increasing the risk of opportunistic infection. There is a critical need to reveal the role of IDU in the immunopathogenesis of HIV infection.

Methods

We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) derived from healthy control (HC) individuals, HIV-infected patients with IDU (HIV-IDU) and without IDU (HIV-nIDU). In addition, the Gene Set Enrichment Analysis (GSEA) was used to analyze the immunomodulatory effects of differential immune cells.

Results

Seven types of cells were identified with specific expressions of maker genes. Specific subsets such as CD14⁺ monocytes, plasmacytoid dendritic cells (pDCs), plasma cells, and CD8⁺ T cells displayed a high degree of heterogeneity among HC, HIV-nIDU, and HIV-IDU. We identified signature genes for each subset in distinct groups, including CFP⁺ CD14⁺ monocytes, PTPRCAP⁺ pDCs, IGHD⁺ plasma cells, and IFITM1⁺ CD8⁺T cells from HIV-IDU, whereas these genes were not expressed in such cells from HIV-nIDU. Moreover, considerable heterogeneity in the function of these immune cells was observed across different groups, especially the elevated IFN-α/β signaling for CD14⁺ monocytes, histone H2A/2B and H3/4 pathway for pDCs, the creation of C4 and C2 activators for plasma cells, and drug metabolism cytochrome p450 for CD8⁺ T cells in HIV-IDU individuals.

Conclusion

Our comprehensive analyses clarify the heterogeneous characteristics of the immune landscape between HIV-IDU and HIV-nIDU. These insights provide a deeper understanding of the IDU-mediated immunopathogenesis in HIV infection.