Single-cell profiling reveals distinct immune response landscapes in tuberculous pleural effusion and non-TPE

Frontiers in Immunology

Immunology

Junhua Pan¹  Rongrong Wei²  Haoran Zhang²  Nanying Che²  Yi Liu²  Xinlei Liao³  Jun Yan³  Guirong Wang³  Chaohong Wang³  Sibo Long³  Maike Zheng³  Yu Xue⁴  Yi Wang⁵  Hangyu Wu⁶  Chong Wang⁶  Qing Sun⁷  Laurence Don Wai Luu⁸  Yun Zhang⁹  Xuelian Li⁹  Qingtao Liang⁹  Xinting Yang⁹  Ru Guo⁹ 

[1] Beijing Chest Hospital, Capital Medical University, Beijing, China;Biobank, Beijing Chest Hospital, Capital Medical University, Beijing, China;Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China;Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, China;Experimental Research Center, Capital Institute of Pediatrics, Beijing, China;Heart Center, Beijing Chest Hospital, Capital Medical University, Beijing, China;National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China;School of Life Sciences, University of Technology Sydney, Sydney, Australia;Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China;

关键词: Mycobacterium tuberculosis;    tuberculosis;    tuberculous pleural effusion;    ScRNA-seq;    local immune response;   

DOI  :  10.3389/fimmu.2023.1191357

 received in 2023-03-22, accepted in 2023-05-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in Mtb-infected tissues is still lacking. Tuberculous pleural effusion (TPE), which is characterized by an influx of immune cells to the pleural space, is thus a suitable platform for dissecting complex tissue responses to Mtb infection.MethodsWe employed singe-cell RNA sequencing to 10 pleural fluid (PF) samples from 6 patients with TPE and 4 non-TPEs including 2 samples from patients with TSPE (transudative pleural effusion) and 2 samples with MPE (malignant pleural effusion).ResultCompared to TSPE and MPE, TPE displayed obvious difference in the abundance of major cell types (e.g., NK, CD4+T, Macrophages), which showed notable associations with disease type. Further analyses revealed that the CD4 lymphocyte population in TPE favored a Th1 and Th17 response. Tumor necrosis factors (TNF)-, and XIAP related factor 1 (XAF1)-pathways induced T cell apoptosis in patients with TPE. Immune exhaustion in NK cells was an important feature in TPE. Myeloid cells in TPE displayed stronger functional capacity for phagocytosis, antigen presentation and IFN-γ response, than TSPE and MPE. Systemic elevation of inflammatory response genes and pro-inflammatory cytokines were mainly driven by macrophages in patients with TPE.ConclusionWe provide a tissue immune landscape of PF immune cells, and revealed a distinct local immune response in TPE and non-TPE (TSPE and MPE). These findings will improve our understanding of local TB immunopathogenesis and provide potential targets for TB therapy.

【 授权许可】

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Copyright © 2023 Yang, Yan, Xue, Sun, Zhang, Guo, Wang, Li, Liang, Wu, Wang, Liao, Long, Zheng, Wei, Zhang, Liu, Che, Luu, Pan, Wang and Wang