Single-cell immune checkpoint landscape of PBMCs stimulated with Candida albicans.
Single-cell immune checkpoint landscape of PBMCs stimulated with Candida albicans.
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DOI：
10.1080/22221751.2021.1942228
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Deng W;Su Z;Liang P;Ma Y;Liu Y;Zhang K;Zhang Y;Liang T;Shao J;Liu X;Han W;Li R
免疫检查点在肿瘤免疫中发挥着多种重要作用，通常会导致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，特别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白色念珠菌（C. albicans）刺激的外周血单核细胞（PBMC）的单细胞RNA测序（scRNA-seq）数据，以探讨白色念珠菌血流感染后免疫检查点的表达模式。我们表征了白色念珠菌感染后不同免疫细胞亚群之间的异质途径活性。 CTLA-4 通路在受刺激的 CD4+ 和 CD8+ T 细胞中上调，而 PD-1 通路在受刺激的浆细胞样树突细胞 (pDC) 和单核细胞中显示出高活性。重要的是，我们发现免疫抑制检查点 HAVCR2 和 LAG3 仅分别在受刺激的 NK 和 CD8+ T 细胞中表达。通过流式细胞术验证了它们的活力。我们还在所有受刺激的细胞中发现了三个过度表达的基因（ISG20、LY6E、ISG15）。本研究还筛选出两个单核细胞特异性过表达基因（SNX10、IDO1）。总之，这些结果补充了真菌感染中免疫检查点的情况，这可能作为白色念珠菌感染的潜在治疗靶点。此外，本研究还鉴定了与白色念珠菌感染最相关的基因。
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 Candida albicans (C. albicans), to explore the expression patterns of immune checkpoints after C. albicans bloodstream infection. We characterized the heterogeneous pathway activities among different immune cell subpopulations after C. albicans 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 HAVCR2 and LAG3 were only expressed in stimulated NK and CD8+ T cells, respectively. Their viabilities were validated by flow cytometry. We also identified three overexpressed genes (ISG20, LY6E, ISG15) across all stimulated cells. Also, two monocyte-specific overexpressed genes (SNX10, IDO1) 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 C. albicans infection. Moreover, the genes with the most relevant for C. albicans infection were identified in this study.