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白色念珠菌刺激的 PBMC 的单细胞免疫检查点图谱

英文原题:Single-cell immune checkpoint landscape of PBMCs stimulated with Candida albicans.

查看英文原题

Single-cell immune checkpoint landscape of PBMCs stimulated with Candida albicans.

PubMed 2021/12/01(内容时间) Emerg Microbes Infect Q1 · IF 7(JCR 2025)

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中文摘要

免疫检查点在肿瘤免疫中发挥着多种重要作用,通常导致T细胞耗竭,从而在肿瘤微环境中引起免疫抑制。然而,免疫检查点在感染性疾病,尤其是真菌感染中的作用仍不明确。

在此,我们重新分析了近期发表的一项经白色念珠菌(C. albicans)刺激的外周血单个核细胞(PBMCs)的单细胞RNA测序(scRNA-seq)数据,以探索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异质性的通路活性。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状细胞(pDC)和单核细胞中表现出高活性。

重要的是,我们发现免疫抑制性检查点HAVCR2和LAG3分别仅在受刺激的NK细胞和CD8+T细胞中表达。其活力通过流式细胞术得到验证。

我们还鉴定出三个在所有受刺激细胞中过表达的基因(ISG20、LY6E、ISG15)。此外,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图谱,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。

展开英文摘要原文

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.

论文信息

作者
Deng W、Su Z、Liang P、Ma Y、Liu Y、Zhang K、Zhang Y、Liang T
单位
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.China
期刊
Emerging microbes & infections2021 Dec
原文标识
PubMed 34120578 · DOI 10.1080/22221751.2021.1942228