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

被引:20
作者
Deng, Weiwei [1 ,2 ,3 ]
Su, Zhen [4 ]
Liang, Panpan [5 ]
Ma, Yubo [1 ,2 ,3 ]
Liu, Yufang [4 ]
Zhang, Kai [1 ,2 ,3 ]
Zhang, Yi [1 ,2 ,3 ]
Liang, Tianyu [1 ,2 ,3 ]
Shao, Jin [1 ,2 ,3 ]
Liu, Xiao [1 ,2 ,3 ]
Han, Wenling [6 ]
Li, Ruoyu [1 ,2 ,3 ]
机构
[1] Peking Univ, Peking Univ First Hosp, Dept Dermatol & Venerol, Beijing, Peoples R China
[2] Natl Clin Res Ctr Skin & Immune Dis, Beijing, Peoples R China
[3] Beijing Key Lab Mol Diag Dermatoses, Beijing, Peoples R China
[4] Sun Yat Sen Univ, Dept Dermatol & Venerol, Affiliated Hosp 3, Guangzhou, Peoples R China
[5] Sun Yat Sen Univ, Clin Lab, Affiliated Hosp 3, Guangzhou, Peoples R China
[6] Peking Univ, Peking Univ Ctr Human Dis Genom, Dept Immunol,Sch Basic Med Sci, Hlth Sci Ctr,Key Lab Med Immunol,Minist Educ, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
Single-cell RNA-sequencing; immune checkpoints; immunotherapy; Candida albicans; bioinformatics; INFECTION; EXPRESSION; THERAPY; CANCER; TIM-3; BLOCKADE; GENES;
D O I
10.1080/22221751.2021.1942228
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1272 / 1283
页数:12
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