02476nas a2200301   4500000000100000008004100001260001200042653001400054653001200068653001400080653001600094100001500110700001400125700001600139700001100155700001500166700001300181700001600194700001500210700001100225700001200236700001500248245007400263300001100337490000800348520180400356022001402160       2022                            d  c04/202210aApoptosis10aleprosy10aM. leprae10aNecroptosis1 ade Sousa J1 aFalcão L1 aVirgolino G1 aCruz M1 aTeixeira V1 aAarão T1 aFurlaneto I1 aCarneiro F1 aAmin G1 aFuzii H1 aQuaresma J00aDifferent cell death mechanisms are involved in leprosy pathogenesis.  a1055110 v1663 a<p>Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.</p>
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