Advances in the pathogenic, genetic and immunological studies of leprosy

Leprosy is an infectious granulomatous disease caused by Mycobacterium leprae that affects the skin and can lead to deformity by damaging peripheral nerves. Although leprosy is no longer an incurable disease, its epidemic has not been well controlled because of its unclear routes of transmission and the lack of an effective vaccine. Moreover, leprosy has long been an ideal disease model for the study of genetics and immunology of infectious diseases due to its strong genetic predisposition and immune-dependent spectrum of clinical manifestations. Here, we review the latest and important findings of the pathogenesis of leprosy. Recent studies have shown that the highly conserved M. leprae is zoonotic, which further complicates the ambiguous transmission of M. leprae. Genetically, genome-wide association studies of leprosy have reported dozens of susceptibility genes, most of which are immune-related, and thus systematically elucidate the immunogenetic basis of the disease. Immunologically, plenty of novel mechanisms of host defense against intracellular bacterial infection and the modulation of host immunity by M. leprae have been depicted. Despite these great achievements, there are still gaps between pathogenic biology, genetics, and immunology of leprosy, limiting our in-depth understanding of leprosy pathogenesis. Further efforts, such as multi-omics data integration and the development of viable animal models for immunogenetic studies are urgently needed to accelerate advances in the precise prevention and treatment of leprosy.