Leprosy is a chronic infectious disease caused by Mycobacterium leprae (ML) affecting the peripheral nerves and skin. The major cause of disabilities observed in leprosy is the result of immunological reactions. These reactional episodes are classified as either reversal reaction (RR) or erythema nodosum leprosum. PS-341 datasheet It is well recognized that cell-mediated immunity is required for an effective response to ML infection. Several studies have established that the production of T helper type 1 cytokines like interferon-γ (IFN-γ) by antigen-specific CD4+ T cells is critical in triggering a protective
immune response against ML. These cells, found in the centre of tuberculoid granuloma, commonly present a memory phenotype. Indeed, ML-specific CD8+ cytotoxic T cells have also been identified in tuberculoid leprosy lesions and appear to benefit their host via granulysin-mediated bacillus killing.[5-7] Reversal reaction, the major cause of the nerve function
impairments resulting in disability and deformity, is characterized by the appearance of new leprosy lesions and the inflammation of existing ones. The immunopathology underlying RR consists of an increased cell-mediated immune response accompanied by CD4+ T cells and macrophage activation in addition to increased expression of pro-inflammatory mediators such as IFN-γ,tumour necrosis factor, interleukins 6, 2 and 12p40, and matrix
SCH772984 concentration metalloproteinases 2 and 9, resulting in an inflammatory response in the skin and peripheral nerves.[8-11] Several lines of evidence suggest that CD4+ ML-responsive T cells with a T helper type 1 phenotype may be responsible for the immune-mediated damage occurring during RR. The impact of HIV infection on the profile of the cell-mediated immune in response to ML is still unknown. Preliminary reports focusing on co-infection suggested that HIV infection 3-oxoacyl-(acyl-carrier-protein) reductase does not affect the clinical classification of leprosy. Although CD4+ T-cell-mediated immunity is compromised in HIV infection, it is broadly accepted that HIV infection does not lead to the multibacillary lepromatous form of the disease, as was previously believed.[14, 15] In a longitudinal study conducted with a cohort of co-infected patients in Brazil, it was noted that 66·7% of the co-infected patients were paucibacillary. In addition, analyses of bacillary loads in multibacillary patients demonstrated that HIV+ patients presented a lower bacillary load than HIV− patients before multidrug therapy, which suggests that co-infected patients tended to have the tuberculoid form and lower bacillary loads. As highly active antiretroviral therapy (HAART) has become more readily available for the treatment of AIDS in countries where leprosy is endemic, more than 40 cases of RR associated with immune reconstitution inflammatory syndrome have been reported.