Leprosy remains a
health problem in several countries. Current management of
patients with
leprosy is complex and requires multidrug
therapy. Nonetheless,
antibiotic treatment is insufficient to prevent nerve disabilities and control
Mycobacterium leprae. Successful
infectious disease treatment demands an
understanding of the host
immune response against a pathogen. Immune-based
therapy is an effective
treatment option for
malignancies and
infectious diseases. A promising
therapeutic approach to improve the clinical outcome of
malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining
self-tolerance and modulating the
immune response. Programmed
cell-
death protein-1 (PD-1),
programmed cell death ligand-1 (PD-L1),
cytotoxic T-lymphocyte-associated
protein 4, and
lymphocyte-activation
gene-3 are the most important
immune checkpoint molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host
immune response.
Regulatory T cells and expression of co-inhibitory molecules on
lymphocytes induce specific
T-cell anergy/exhaustion, leading to disseminated and progressive
disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/
Treg cells are balanced, how
antigen-presenting cell maturation acts at different levels to inhibit
T cells and modulate the development of
leprosy, and how new interventions interfere with
leprosy development.