The expression of PD-1 and its ligands increases in Leishmania infection and its blockade reduces the parasite burden. (May 2022)

• Record Type: Journal Article
• Authors: Jafarzadeh, Abdollah; Kumar, Sunil; Bodhale, Neelam; Jafarzadeh, Sara; Nemati, Maryam; Sharifi, Iraj; Sarkar, Arup; Saha, Bhaskar
• Is Part Of: Cytokine. Volume 153(2022)
• Publication Date: 2022-05
• Subjects: Leishmaniasis -- Immune responses -- Programmed death-1 -- PD-L1 -- PD-L2 -- T cell exhaustion; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2022.155839
• Languages: English
• ISSNs: 1043-4666

Abstract

Abstract: The expression of programmed cell death protein-1 (PD-1) and its ligands- PD-L1 and PD-L2- on T cells and macrophages', respectively, increases in Leishmania infection. The PD-1/PD-L1 interaction induces T cell anergy, T cell apoptosis and exhaustion, diversion of T cells toward TH 2 and T-reg cells but inhibits M1 macrophage activities by suppression of nitric oxide (NO) and reactive oxygen species (ROS) production. These changes exacerbate Leishmania infection. As PD-L1-deficient, but not PD-L2-deficient, mice were protected against L. mexicana infection, differential roles have been proposed for PD-L1 and PD-L2 in mouse models of leishmaniasis. Blockade of PD-1/PD-L1 interaction in various in vitro and Leishmania- infected mouse, hamster and dog models enhanced IFN-γ and NO production, reduced IL-10 and TGF-β generation, promoted T cell proliferation and reduced parasite burden. Therefore, PD-1/PD-L1 blockade is being considered as a potential therapeutic strategy to restore protective immunity during leishmaniasis, particularly, in drug-resistant cases.