Department of Dermatology and Venerology, Peking University First Hospital, Peking University; National Clinical Research Center for Skin and Immune Diseases; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing, People's Republic of China.
Department of Dermatology and Venerology, The Third Affiliated Hospital of Sun Yat-Sen university, Guangzhou, People's Republic of China.
Emerg Microbes Infect. 2021 Dec;10(1):1272-1283. doi: 10.1080/22221751.2021.1942228.
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 (), to explore the expression patterns of immune checkpoints after bloodstream infection. We characterized the heterogeneous pathway activities among different immune cell subpopulations after 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 and were only expressed in stimulated NK and CD8 T cells, respectively. Their viabilities were validated by flow cytometry. We also identified three overexpressed genes (, , ) across all stimulated cells. Also, two monocyte-specific overexpressed genes (, ) 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 infection. Moreover, the genes with the most relevant for infection were identified in this study.
免疫检查点在肿瘤免疫中发挥着各种重要作用,通常导致 T 细胞耗竭,从而导致肿瘤微环境中的免疫抑制。然而,免疫检查点在传染病中的作用,尤其是真菌感染中的作用仍然难以捉摸。在这里,我们重新分析了最近发表的一项外周血单个核细胞(PBMC)经 刺激的单细胞 RNA 测序(scRNA-seq)数据[1],以探索 血流感染后免疫检查点的表达模式。我们描述了感染后不同免疫细胞亚群中异质途径活性。CTLA-4 途径在刺激的 CD4 和 CD8 T 细胞中上调,而 PD-1 途径在刺激的浆细胞样树突状细胞(pDC)和单核细胞中表现出高活性。重要的是,我们发现抑制性免疫检查点 和 仅在刺激的 NK 和 CD8 T 细胞中表达,其活力通过流式细胞术得到验证。我们还鉴定出所有刺激细胞中均过表达的三个基因(、、)。此外,本研究还筛选出两个单核细胞特异性过表达基因(、)。总之,这些结果补充了真菌感染中免疫检查点的全景图,它们可能成为 感染的潜在治疗靶点。此外,本研究还鉴定出与 感染最相关的基因。