Metabolic, Genetic and Immunological Mechanisms in Susceptibility to Leprosy

In the past decade, the availability of data obtained from large-scale studies using molecular and genetic techniques has provided a much-improved picture of the main pathogenic pathways involved in the progression of leprosy. There is a clear clustering of genes encoding for hallmark immune response molecules, reinforcing the overall understanding of the immunopathogenic processes leading to leprosy susceptibility or to polarization between clinical phenotypes. Metabolic changes, cellular trafficking, and autophagy regulate the responses to confer protection and eliminate bacilli from the host. Alternatively, in hosts that are susceptible due to genetic and/or environmental conditions, immune cells fail to activate this protective program through the interference of M. leprae ultimately leading to disease development. Recent insights on the immunopathology of leprosy can pave the way for new diagnostics and personalized therapy based on the immune profile of the specific clinical form of the disease.