Single-cell immune checkpoint landscape of PBMCs stimulated with <i>Candida albicans</i>

Immune checkpoints play various important roles in tumour immunity, which usually contribute to T cells’ exhaustion, leading to immunosuppression in the tumour microenvironment. However, the roles of immune checkpoints in infectious diseases, especially fungal infection, remain elusive. Here, we reanalyzed a recent published single-cell RNA-sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) stimulated with <i>Candida albicans</i> (<i>C. albicans</i>), to explore the expression patterns of immune checkpoints after <i>C. albicans</i> bloodstream infection. We characterized the heterogeneous pathway activities among different immune cell subpopulations after <i>C. albicans</i> infection. The CTLA-4 pathway was up-regulated in stimulated CD4⁺ and CD8⁺ T cells, while the PD-1 pathway showed high activity in stimulated plasmacytoid dendritic cell (pDC) and monocytes. Importantly, we found that immunosuppressive checkpoints <i>HAVCR2</i> and <i>LAG3</i> were only expressed in stimulated NK and CD8⁺ T cells, respectively. Their viabilities were validated by flow cytometry. We also identified three overexpressed genes (<i>ISG20</i>, <i>LY6E</i>, <i>ISG15</i>) across all stimulated cells. Also, two monocyte-specific overexpressed genes (<i>SNX10</i>, <i>IDO1</i>) were screened out in this study. Together, these results supplemented the landscape of immune checkpoints in fungal infection, which may serve as potential therapeutic targets for <i>C. albicans</i> infection. Moreover, the genes with the most relevant for <i>C. albicans</i> infection were identified in this study.