PD-L1 Expression in Monocytes Correlates with Bacterial Burden and Treatment Outcomes in Active Pulmonary Tuberculosis

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1619
• Main Authors: Pan, Sheng-Wei, Shu, Chin-Chung, Huang, Jhong-Ru, Lee, Chang-Ching, Tseng, Yen-Han, Hung, Jung-Jyh, Hsu, Po-Kuei, Chen, Nien-Jung, Su, Wei-Juin, Feng, Jia-Yih, Chen, Yuh-Min
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; B7-H1 Antigen - metabolism; Case-Control Studies; CD14 antigen; CD4 antigen; Cell culture; Cells, Cultured; Clinical outcomes; Disease Models, Animal; Female; Fever; Humans; Immunofluorescence; Immunohistochemistry; Infections; Latent Tuberculosis - metabolism; Latent Tuberculosis - microbiology; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Ligands; Lungs; Lymphocytes; Lymphocytes T; Macrophages; Male; Mice; Middle Aged; Monocytes; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - pathogenicity; Pathogenesis; Patients; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Peripheral blood mononuclear cells; Programmed Cell Death 1 Receptor - metabolism; Proteins; pulmonary tuberculosis; Sputum; THP-1 Cells; Treatment Outcome; treatment outcomes; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - microbiology; Up-Regulation; Viral infections; Young Adult
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031619

The PD-1/PD-L1 pathway is critical in T cell biology; however, the role of the PD-1/PD-L1 pathway in clinical characteristics and treatment outcomes in pulmonary tuberculosis (PTB) patients is unclear. We prospectively enrolled PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects. The expression of PD-1/PD-L1 on peripheral blood mononuclear cells (PBMCs) was measured and correlated with clinical characteristics and treatment outcomes in PTB patients. Immunohistochemistry and immunofluorescence were used to visualize PD-1/PD-L1-expressing cells in lung tissues from PTB patients and from murine with heat-killed MTB (HK-MTB) treatment. A total of 76 PTB, 40 LTBI, and 28 non-TB, non-LTBI subjects were enrolled. The expression of PD-1 on CD4+ T cells and PD-L1 on CD14+ monocytes was significantly higher in PTB cases than non-TB subjects. PTB patients with sputum smear/culture unconversion displayed higher PD-L1 expression on monocytes. PD-L1-expressing macrophages were identified in lung tissue from PTB patients, and co-localized with macrophages in murine lung tissues. (MTB) whole cell lysate/EsxA stimulation of human and mouse macrophages demonstrated increased PD-L1 expression. In conclusion, increased expression of PD-L1 on monocytes in PTB patients correlated with higher bacterial burden and worse treatment outcomes. The findings suggest the involvement of the PD-1/PD-L1 pathway in MTB-related immune responses.