Pan Jiahui, Zhang Xinyue, Xu Jianting, Chang Zecheng, Xin Zhuoyuan, Wang Guoqing
Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun, China.
The First Hospital of Jilin University, Changchun, China.
Microbiol Spectr. 2023 Mar 14;11(2):e0283922. doi: 10.1128/spectrum.02839-22.
Tuberculosis, a contagious bacterial infection caused by Mycobacterium tuberculosis, is a substantial global health problem, impacting millions of lives annually. Exhausted T-cell signatures are critical for predicting clinical responses to tuberculosis infection. To obtain a panoramic transcriptional profile of T cells, we performed single-cell RNA-sequencing analysis of CD4 T and CD8 T cells isolated from peripheral blood mononuclear cells of healthy individuals and patients with tuberculosis. We identified seven subsets in CD8 T cells and eight subsets in CD4 T cells and elucidated the transcriptomic landscape changes and characteristics of each subset. We further investigated the cell-to-cell relationship of each subgroup of the two cell types. Different signature genes and pathways of exhausted CD4 and CD8 T cells were examined. We identified 12 genes with potential associations of T-cell exhaustion after tuberculosis infection. We also identified five genes as potential exhaustion marker genes. The CD8-EX3 subcluster in CD8 T-exhausted cells was identified as an exhaustion-specific subcluster. The identified gene module further clarified the key factors influencing CD8 T cell exhaustion. These data provide new insights into T-cell signatures in tuberculosis-exhausted populations. Identifying the changes in immune cells in response to infection can provide a better understanding of the effects of Mycobacterium tuberculosis on the host immune system. We performed single-cell RNA-sequencing analysis of CD4 T and CD8 T cells isolated from peripheral blood mononuclear cells of healthy individuals and patients with tuberculosis to reveal the cellular characteristics. Different signature genes and pathways of exhausted CD4 and CD8 T cells were examined. These will facilitate a more comprehensive understanding of the onset and underlying mechanism of T-cell exhaustion during active infection.
结核病是一种由结核分枝杆菌引起的传染性细菌感染，是一个重大的全球健康问题，每年影响数百万人的生命。耗竭的T细胞特征对于预测结核病感染的临床反应至关重要。为了获得T细胞的全景转录图谱，我们对从健康个体和结核病患者外周血单核细胞中分离出的CD4 T细胞和CD8 T细胞进行了单细胞RNA测序分析。我们在CD8 T细胞中鉴定出七个亚群，在CD4 T细胞中鉴定出八个亚群，并阐明了每个亚群的转录组景观变化和特征。我们进一步研究了这两种细胞类型各亚组之间的细胞间关系。检测了耗竭的CD4和CD8 T细胞的不同特征基因和信号通路。我们鉴定出12个与结核病感染后T细胞耗竭可能相关的基因。我们还鉴定出五个基因作为潜在的耗竭标记基因。CD8 T耗竭细胞中的CD8-EX3亚簇被鉴定为一个耗竭特异性亚簇。所鉴定的基因模块进一步阐明了影响CD8 T细胞耗竭的关键因素。这些数据为结核病耗竭人群中的T细胞特征提供了新的见解。识别免疫细胞对感染的反应变化可以更好地理解结核分枝杆菌对宿主免疫系统的影响。我们对从健康个体和结核病患者外周血单核细胞中分离出的CD4 T细胞和CD8 T细胞进行了单细胞RNA测序分析，以揭示细胞特征。检测了耗竭的CD4和CD8 T细胞的不同特征基因和信号通路。这些将有助于更全面地了解活动性感染期间T细胞耗竭的发生及潜在机制。
