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

Sheng Wei Pan, Chin Chung Shu, Jhong Ru Huang, Chang Ching Lee, Yen Han Tseng, Jung Jyh Hung, Po Kuei Hsu, Nien Jung Chen, Wei Juin Su, Jia Yih Feng*, Yuh Min Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. Mycobacterium tuberculosis (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.

Original languageEnglish
Article number1619
JournalInternational Journal Of Molecular Sciences
Volume23
Issue number3
DOIs
StatePublished - 1 Feb 2022

Keywords

  • Macrophages
  • PD-1
  • PD-L1
  • Pulmonary tuberculosis
  • Treatment outcomes

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