Abstract
Leprosy, a disease caused by the intracellular parasite Mycobacterium leprae or Mycobacterium lepromatosis, has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model for studying the interaction between host immune response and infection; in fact, the landscape of leprosy immune responses has been extensively investigated. Meanwhile, leprosy is to some extent a genetic disease because the genetic factors of hosts have long been considered major contributors to this disease. Many immune-related genes have been discovered to be associated with leprosy. However, immunological and genetic findings have rarely been studied and discussed together, and as a result, the effects of gene variants on leprosy immune responses and the molecular mechanisms of leprosy pathogenesis are largely unknown. In this context, we summarized advances in both the immunology and genetics of leprosy and discussed the perspective of the combination of immunological and genetic approaches in studying the molecular mechanism of leprosy pathogenesis. In our opinion, the integrating of immunological and genetic approaches in the future may be promising to elucidate the molecular mechanism of leprosy onset and how leprosy develops into different types of leprosy.
Highlights
Leprosy is an ancient disease caused by Mycobacterium leprae or Mycobacterium lepromatosis infection, which mainly impairs skin and peripheral nerves and can even result in disability [1]
Based on the different immune responses observed in patient lesions, leprosy can be categorized into five groups: tuberculoid (TT), borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), and lepromatous (LL) [5]
Combining this genetic finding with the expression of PARK2 and PACRG in macrophages and Schwann cells, the authors pointed out that ubiquitin-mediated proteolysis might function in leprosy pathogenesis, but this association signal was not observed in Indians or Chinese [161, 162]
Summary
Leprosy is an ancient disease caused by Mycobacterium leprae or Mycobacterium lepromatosis infection, which mainly impairs skin and peripheral nerves and can even result in disability [1]. The authors demonstrated a significantly higher level of IL-1β in the serum of T1R group months before T1R onset, suggesting IL-1β as a potential marker for T1R prediction [20] Another canonical antimicrobial pathway, the nitric oxide (NO) antimicrobial pathway, was studied by a quantitative analysis of inducible NO synthase (iNOS) expression in polar forms of leprosy [21]. The interaction of PGL-I with CR3 promoted the invasion of the bacteria into these innate cells and selectively increased the production of IL-2 by DCs, IL-10 by PMNs, and IL1β by macrophages, respectively, through the CR3–Syk–NFATc axis [25] These studies demonstrated how the virulence factor of M. leprae PGL-I shaped the innate immune responses of innate cells, which may eventually effect the clinical symptoms of leprosy.
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