Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis
Authors:Yen-Han Tseng1,2, Sheng-Wei Pan1,2,3, Jhong-Ru Huang2,4, Chang-Ching Lee1, Jung-Jyh Hung2,5, Po-Kuei Hsu2,5, Nien-Jung Chen6, Wei-Juin Su2,7, Yuh-Min Chen1,2 and Jia-Yih Feng1,2,8
doi: 10.15698/mic2024.07.832
Volume 11, pp. 277 to 287, published 29/07/2024.
1 Department of Chest Medicine, Taipei Veterans General Hospital, 112, Taipei, Taiwan. 2 School of Medicine, National Yang Ming Chiao Tung University, 112, Taipei, Taiwan. 3 Institute of Public Health, National Yang Ming Chiao Tung University, 112, Taipei, Taiwan. 4 Division of Chest Medicine, Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan. 5 Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112, Taiwain. 6 Institute of Microbiology and Immunology, School of Life Sciences, National Yang Ming Chiao Tung University, 112, Taipei, Taiwan. 7 Division of Chest Medicine, China Medical University Hospital, Taipei Branch, Taipei, 114, Taiwan. 8 Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, 112, Taipei, Taiwan.
Keywords:
methylation, PD-L1, pulmonary tuberculosis, macrophages, treatment outcomes.
Corresponding Author(s):
Conflict of interest statement:
The authors of this article declare that they do not have any conflict of interest.
Please cite this article as:
Yen-Han Tseng, Sheng-Wei Pan, Jhong-Ru Huang, Chang-Ching Lee, Jung-Jyh Hung, Po-Kuei Hsu, Nien-Jung Chen, Wei-Juin Su, Yuh-Min Chen, Jia-Yih Feng (2024). Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis. Microbial Cell 11: 278-287. doi: 10.15698/mic2024.07.832
© 2024 Tseng et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of Mycobacterium tuberculosis (MTB) infection. DNA methylation is a mechanism that modulates PD-L1 expression in cancer cells. However, its effect on PD-L1 expression in macrophages after MTB infection remains unknown. We prospectively enrolled patients with active tuberculosis (TB) and non-TB subjects. The expression of PD-L1 and methylation-related genes in peripheral blood mononuclear cells (PBMCs) were investigated and their correlation with disease severity and treatment outcomes were examined. PD-L1 promoter methylation status was evaluated using bisulfite sequencing. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to visualize PD-L1- and TET-1-expressing cells in lung tissues from patients with TB and in macrophage cell lines with MTB-related stimulation. In total, 80 patients with active TB and 40 non-TB subjects were enrolled in the analysis. Patients with active TB had significantly higher expression of PD-L1, DNMT3b, TET1, TET2, and lower expression of DNMT1, compared to that in the non-TB subjects. The expression of PD-L1 and TET-1 was significantly associated with 1-month smear and culture non-conversion. IHC and IF staining demonstrated the co-localization of PD-L1- and TET-1-expressing macrophages in patients with pulmonary TB and in human macrophage cell lines after MTB-related stimulation. DNMT inhibition and TET-1 knockdown in human macrophages increased and decreased PD-L1 expression, respectively. Overall, PD-L1 expression is increased in patients with active TB and is correlated with treatment outcomes. DNA methylation is involved in modulating PD-L1 expression in human macrophages.