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

Xinting Yang; Jun Yan; Yu Xue; Qing Sun; Yun Zhang; Ru Guo; Chaohong Wang; Xuelian Li; Qingtao Liang; Hangyu Wu; Chong Wang; Xinlei Liao; Sibo Long; Maike Zheng; Rongrong Wei; Haoran Zhang; Yi Liu; Nanying Che; Laurence Don Wai Luu; Junhua Pan; Guirong Wang; Yi Wang

doi:10.3389/fimmu.2023.1191357

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

Front Immunol. 2023 Jun 26:14:1191357. doi: 10.3389/fimmu.2023.1191357. eCollection 2023.

Authors

Xinting Yang¹, Jun Yan², Yu Xue³, Qing Sun⁴, Yun Zhang¹, Ru Guo¹, Chaohong Wang², Xuelian Li¹, Qingtao Liang¹, Hangyu Wu⁵, Chong Wang⁵, Xinlei Liao², Sibo Long², Maike Zheng², Rongrong Wei⁶, Haoran Zhang⁶, Yi Liu⁶, Nanying Che⁶, Laurence Don Wai Luu⁷, Junhua Pan⁸, Guirong Wang², Yi Wang⁹

Affiliations

¹ Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
² Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
³ Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁴ 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.
⁵ Heart Center, Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁶ Biobank, Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁷ School of Life Sciences, University of Technology Sydney, Sydney, Australia.
⁸ Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁹ Experimental Research Center, Capital Institute of Pediatrics, Beijing, China.

Abstract

Background: Tuberculosis (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.

Methods: We 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).

Result: Compared 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.

Conclusion: We 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.

Keywords: Mycobacterium tuberculosis; ScRNA-seq; local immune response; tuberculosis; tuberculous pleural effusion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigen Presentation
Humans
Mycobacterium tuberculosis*
Pleural Cavity
Pleural Effusion*
Tuberculosis*

Grants and funding

This work was supported by grants from National Key Research and Development Program of China (Grant Nos. 2021YFC2301101, 2021YFC2301102), Capital’s Funds for Health Improvement and Research (2022-1G-2162), Beijing Public Health Experts Project (2022-3-040), Key Project of the Department of Science and Technology, Beijing, China (Grant Nos.D181100000418003, Z191100006619078). National Natural Science Foundation of China (82100011), LL was supported by a UTS Chancellor’s Postdoctoral Research Fellowship.