Single-cell transcriptomics of blood reveals a natural killer cell subset depletion in tuberculosis
Yi Cai,
Youchao Dai,
Yejun Wang,
Qianqing Yang,
Jiubiao Guo,
Cailing Wei,
Weixin Chen,
Huanping Huang,
Jialou Zhu,
Chi Zhang,
Weidong Zheng,
Zhihua Wen,
Haiying Liu,
Mingxia Zhang,
Shaojun Xing,
Qi Jin,
Carl G. Feng,
Xinchun Chen
Affiliations
Yi Cai
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Youchao Dai
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China; Research Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510000, China
Yejun Wang
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Qianqing Yang
Guangdong Key Lab for Diagnosis &Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518000, China
Jiubiao Guo
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Cailing Wei
Guangdong Key Lab for Diagnosis &Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518000, China
Weixin Chen
Guangdong Key Lab for Diagnosis &Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518000, China
Huanping Huang
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Jialou Zhu
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Chi Zhang
Shenzhen University General Hospital, Shenzhen University School of Medicine, Shenzhen 518000, China
Weidong Zheng
Shenzhen University General Hospital, Shenzhen University School of Medicine, Shenzhen 518000, China
Zhihua Wen
Yuebei Second People's Hospital, Shaoguan 512000, China
Haiying Liu
The MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100176, China
Mingxia Zhang
Guangdong Key Lab for Diagnosis &Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518000, China
Shaojun Xing
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
Qi Jin
The MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Centre for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100176, China
Carl G. Feng
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China; Department of Infectious Diseases and Immunology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia
Xinchun Chen
Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China; Corresponding author.
Background: Tuberculosis (TB) continues to be a critical global health problem, which killed millions of lives each year. Certain circulating cell subsets are thought to differentially modulate the host immune response towards Mycobacterium tuberculosis (Mtb) infection, but the nature and function of these subsets is unclear. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls (HC), latent tuberculosis infection (LTBI) and active tuberculosis (TB) and then subjected to single-cell RNA sequencing (scRNA-seq) using 10 × Genomics platform. Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Flow cytometry was used to validate the subsets identified by scRNA-Seq. Findings: Cluster analysis based on differential gene expression revealed both known and novel markers for all main PBMC cell types and delineated 29 cell subsets. By comparing the scRNA-seq datasets from HC, LTBI and TB, we found that infection changes the frequency of immune-cell subsets in TB. Specifically, we observed gradual depletion of a natural killer (NK) cell subset (CD3-CD7+GZMB+) from HC, to LTBI and TB. We further verified that the depletion of CD3-CD7+GZMB+ subset in TB and found an increase in this subset frequency after anti-TB treatment. Finally, we confirmed that changes in this subset frequency can distinguish patients with TB from LTBI and HC. Interpretation: We propose that the frequency of CD3-CD7+GZMB+ in peripheral blood could be used as a novel biomarker for distinguishing TB from LTBI and HC. Fund: The study was supported by Natural Science Foundation of China (81770013, 81525016, 81772145, 81871255 and 91942315), National Science and Technology Major Project (2017ZX10201301), Science and Technology Project of Shenzhen (JCYJ20170412101048337) and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Keyword: Tuberculosis, Single-cell RNA sequencing, CD3-CD7+GZMB+, NK cells
