Pathogenesis and Host Immune Response in Leprosy

Leprosy is an ancient insidious disease caused by Mycobacterium leprae, where the skin and peripheral nerves undergo chronic granulomatous infections, leading to sensory and motor impairment with characteristic deformities. Susceptibility to leprosy and its disease state are determined by the manifestation of innate immune resistance mediated by cells of monocyte lineage. Due to insufficient innate resistance, granulomatous infection is established, influencing the specific cellular immunity. The clinical presentation of leprosy ranges between two stable polar forms (tuberculoid to lepromatous) and three unstable borderline forms. The tuberculoid form involves Th1 response, characterized by a well demarcated granuloma, infiltrated by CD4⁺ T lymphocytes, containing epitheloid and multinucleated giant cells. In the lepromatous leprosy, there is no characteristic granuloma but only unstructured accumulation of ineffective macrophages containing engulfed pathogens. Th1 response, characterised by IFN-γ and IL-2 production, activates macrophages in order to kill intracellular pathogens. Conversely, a Th2 response, characterized by the production of IL-4, IL-5 and IL-10, helps in antibody production and consequently downregulates the cell-mediated immunity induced by the Th1 response. M. lepare has a long generation time and its inability to grow in culture under laboratory conditions makes its study challenging. The nine-banded armadillo still remains the best clinical and immunological model to study host-pathogen interaction in leprosy. In this chapter, we present cellular morphology and the genomic uniqueness of M. leprae, and how the pathogen shows tropism for Schwann cells, macrophages and dendritic cells.