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

Lin Wang; Hui Ma; Zilu Wen; Liangfei Niu; Xinchun Chen; Haiying Liu; Shulin Zhang; Jianqing Xu; Yijun Zhu; Hongwei Li; Hui Chen; Lei Shi; Laiyi Wan; Leilei Li; Meiyi Li; Ka-Wing Wong; Yanzheng Song

doi:10.1016/j.jinf.2023.09.004

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

J Infect. 2023 Nov;87(5):373-384. doi: 10.1016/j.jinf.2023.09.004. Epub 2023 Sep 9.

Authors

Lin Wang¹, Hui Ma², Zilu Wen², Liangfei Niu², Xinchun Chen³, Haiying Liu⁴, Shulin Zhang², Jianqing Xu², Yijun Zhu¹, Hongwei Li¹, Hui Chen¹, Lei Shi¹, Laiyi Wan¹, Leilei Li¹, Meiyi Li⁵, Ka-Wing Wong⁶, Yanzheng Song⁷

Affiliations

¹ Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Shanghai, China.
² Department of Scientific Research, Shanghai Public Health Clinical Center, Shanghai, China.
³ Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China.
⁴ 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.
⁵ Fudan Zhangjiang Institute, Fudan University, Shanghai, China. Electronic address: limeiyi@sibs.ac.cn.
⁶ Department of Scientific Research, Shanghai Public Health Clinical Center, Shanghai, China. Electronic address: kwwong@gmail.com.
⁷ Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Shanghai, China. Electronic address: yanzhengsong@163.com.

PMID: 37690670
DOI: 10.1016/j.jinf.2023.09.004

Abstract

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.

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