Single-cell RNA-sequencing reveals heterogeneity and intercellular crosstalk in human tuberculosis lung - 21/09/23

Doi : 10.1016/j.jinf.2023.09.004

Lin Wang ^a,^{^{1
These authors contributed equally}}, Hui Ma ^b,^{^{1
These authors contributed equally}}, Zilu Wen ^b,^{^{1
These authors contributed equally}}, Liangfei Niu ^b, Xinchun Chen ^c, Haiying Liu ^d, Shulin Zhang ^b, Jianqing Xu ^b, Yijun Zhu ^a, Hongwei Li ^a, Hui Chen ^a, Lei Shi ^a, Laiyi Wan ^a, Leilei Li ^a, Meiyi Li ^e,^⁎ , Ka-Wing Wong ^b,^⁎ , Yanzheng Song ^a,^⁎
^a Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Shanghai, China
^b Department of Scientific Research, Shanghai Public Health Clinical Center, Shanghai, China
^c Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China
^d NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
^e Fudan Zhangjiang Institute, Fudan University, Shanghai, China

^⁎Corresponding authors.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 21 September 2023
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Summary

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.

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Highlights

•	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.

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Keywords : Single-cell RNA-sequencing, Pulmonary tuberculosis lesion, 18F-FDG avidity, Cellular heterogeneity and crosstalk