Mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview

Abstract

Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae-host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed.

Figure 1. Lepromatous macrophages have increased expression and activity of IDO that is probably induced by mycobacterial components of cytokines such as TNF or IFN-γ

Increased IL-10 and PGE₂ levels were observed in LL macrophages. LL macrophages also present increased expression of the scavenger receptor CD163 and oxidized phospholipids, which is related to PPAR-γ induction by the mycobacteria. By contrast, in tuberculoid macrophages the decrease in IDO expression was probably due to increased nitric oxide and other reactive radicals, which may contribute to the control of bacillary load. IDO: Indoleamine-pyrrole 2,3-dioxygenase; LL: Lepromatous leprosy; NO: Nitric oxide; OxPL: Oxidized phospholipid; PGE₂: Prostaglandin E2.