Differential expression of programmed death 1 (PD-1) on various immune cells and its role in human leprosy

Mohammad Tarique, Huma Naz, Mohd Suhail, Ali Turan, Chaman Saini, Naoshad Muhammad, Hari Shankar, Torki A. Zughaibi, Tabish H. Khan, Neena Khanna, Alpana Sharma

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Leprosy is a chronic bacterial disease caused by Mycobacterium leprae. Leprosy patients have been found to have defects in T cells activation, which is critical to the clearance of the bacilli. Treg cell suppression is mediated by inhibitory cytokines such as IL10, IL-35 and TGF-β and its frequency is higher in leprosy patients. Activation and overexpression of programmed death 1 (PD-1) receptor is considered to one of the pathways to inhibit T-cell response in human leprosy. In the current study we address the effect of PD-1 on Tregs function and its immuno-suppressive function in leprosy patients. Flow cytometry was used to evaluate the expression of PD-1 and its ligands on various immune cells T cells, B cells, Tregs and monocytes. We observed higher expression of PD-1 on Tregs is associated with lower production of IL-10 in leprosy patients. PD-1 ligands on T cells, B cells, Tregs and monocytes found to be higher in the leprosy patients as compared to healthy controls. Furthermore, in vitro blocking of PD-1 restores the Tregs mediated suppression of Teff and increase secretion of immunosuppressive cytokine IL-10. Moreover, overexpression of PD-1 positively correlates with disease severity as well as Bacteriological Index (BI) among leprosy patients. Collectively, our data suggested that PD-1 overexpression on various immune cells is associated with disease severity in human leprosy. Manipulation and inhibition of PD-1 signaling pathway on Tregs alter and restore the Treg cell suppression activity in leprosy patients.

Original languageEnglish
Article number1138145
JournalFrontiers in immunology
Volume14
DOIs
StatePublished - 2023

Keywords

  • IL-10
  • leprosy
  • PD-1
  • T cell anergy
  • T cells
  • Tregs

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