免疫失调
细胞毒性T细胞
肺结核
免疫系统
CD8型
医学
穿孔素
颗粒酶
免疫学
结核分枝杆菌
T细胞
生物
病理
生物化学
体外
作者
Yi Wang,Qing Sun,Yun Zhang,Xuelian Li,Qingfeng Liang,Ru Guo,L.‐Q. Zhang,Xiqin Han,Jing Wang,Lingling Shao,Yu Xue,Yang Yang,Hua Li,Lihui Nie,Wenhui Shi,Qiuyue Liu,Jing Zhang,Hongfei Duan,Hairong Huang,Laurence Don Wai Luu,Jun Tai,Xinting Yang,Guirong Wang
标识
DOI:10.1016/j.jinf.2023.03.020
摘要
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.
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