New findings in the pathogenesis of leprosy and implications for the management of leprosy

Abstract

Novel biological pathways have been identified to be associated with the clinical phenotype of leprosy or the occurrence of leprosy reactions. Future work should include larger numbers of clinical samples from across the leprosy spectrum in order to give new insights in the pathogenesis and management of the disease.

Leprosy in the 21st Century

“…The traditional model of interaction of an infectious agent that includes host, pathogen, and environment is a unique one in the case of HD. Overall, there seems to be little pathogen variability and virulence to explain the different clinical forms, with the possible exception of the recently discovered species Mycobacterium lepromatosis in patients with HD who had diffuse leprosy of Lucio and Latapí (3,19,20). Confirmation of this as a new species that could cause HD requires further research, as defined by Gillis et al (21).…”

“…Confirmation of this as a new species that could cause HD requires further research, as defined by Gillis et al (21). However, most of the clinical phenotypes may be due to genetic variability determined by different biological pathways modulated by M. leprae and reprogramming of adult Schwann cells and interactions of innate and adaptive immunity (3,8).…”

“…This transformation creates a suitable environment for the bacteria to proliferate (7). More recently, it has been shown that further dedifferentiation leads to the reprogramming the Schwann cell to a "stem cell-like" cell with a plethora of new capabilities, such as redifferentiation into mesenchymal cells with the ability to spread infection or attracting macrophages to develop granulomas that could then serve as a Trojan horse for systemic dissemination of M. leprae (3,8). The presence of bacilli in the skin produces the dermatological manifestations of the disease, and nerve infection produces axonal dysfunction and demyelination, leading to sensory loss and its consequences of disability and deformity (2,9).…”

“…HD results from infection with the Mycobacterium leprae bacillus, which produces a chronic infection in humans that affects mainly peripheral nerves and skin but may also affect sites such as the eyes, mucous membranes, bones, and testes and produces a spectrum of clinical phenotypes (1)(2)(3). In the skin, M. leprae has an affinity for keratinocytes, macrophages, and histiocytes (3,4).…”

Importance of the immune response to Mycobacterium leprae in the skin

“…The most recent studies have included interferon (Teles et al 2013), vitamin D-dependent antimicrobial pathways (Liu et al 2012), NOD2-mediated signalling (Netea et al 2010) and the role of T regulatory cells, Th-17/IL17a/IL-17F cytokines, CD163 and galectin-3 (Polycarpou et al 2013). A deeper understanding of the M. leprae genome will provide insight into the mechanism by which this organism avoids immune surveillance.…”