Single-cell RNA-sequencing reveals heterogeneity and intercellular crosstalk in human tuberculosis lung

• Published in: The Journal of infection Vol. 87; no. 5; pp. 373 - 384
• Main Authors: Wang, Lin, Ma, Hui, Wen, Zilu, Niu, Liangfei, Chen, Xinchun, Liu, Haiying, Zhang, Shulin, Xu, Jianqing, Zhu, Yijun, Li, Hongwei, Chen, Hui, Shi, Lei, Wan, Laiyi, Li, Leilei, Li, Meiyi, Wong, Ka-Wing, Song, Yanzheng
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2023
• Subjects: 18F-FDG avidity; Cellular heterogeneity and crosstalk; Pulmonary tuberculosis lesion; Single-cell RNA-sequencing; 18F-FDG avidity; Single-cell RNA-sequencing; Cellular heterogeneity and crosstalk; Pulmonary tuberculosis lesion
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2023.09.004

Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients with tuberculosis is associated with disease severity and relapse risk upon treatment completion. We revealed the heterogeneity and intercellular crosstalk in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6 tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells in inflamed lungs showed general up-regulation of ATP synthesis and interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly displayed transcriptions of genes related to tuberculosis disease progression. Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells involving chemokines, costimulatory molecules, and immune checkpoints, some of which are specific in 18F-FDG-avid lungs, were found. Our analysis provides insights into the transcriptomic heterogeneity and cellular crosstalk in pulmonary tuberculosis and guides unveiling cellular and molecular targets for tuberculosis therapy. •Single-cell RNA sequencing reveals cellular landscape in inflamed human TB lungs.•Inflamed TB lungs show disease-linked transcriptional changes in myeloid and Treg cells.•Treg cells and immunosuppressive myeloid cells feature extensive crosstalk potential.