Expression of nlrp3 inflammasome in leprosy indicates immune evasion of mycobacterium leprae

Abstract

BACKGROUND Leprosy is an infectious-contagious disease caused by Mycobacterium leprae that remain endemic in 105 countries. This neglected disease has a wide range of clinical and histopathological manifestations that are related to the host inf lammatory and immune responses. More recently, the inf lammasome has assumed a relevant role in the inf lammatory response against microbiological agents. However, the involvement of inf lammasome in leprosy remains poorly understood. OBJECTIVES The aim is to associate biomarkers of inf lammasome with the different immunopathological forms of leprosy. METHODS We performed an observational, cross-sectional, and comparative study of the immunophenotypic expression of inf lammasome-associated proteins in immunopathological forms of leprosy of 99 skin lesion samples by immunohistochemistry. The intensity and percentage of NLRP3, Caspase-1, Caspases-4/5, interleukin-1β and interleukin-18 immunoreactivities in the inf lammatory infiltrate of skin biopsies were evaluated. FINDINGS Strong expression of NLRP3 and inf lammatory Caspases-4/5 were observed in lepromatous leprosy (lepromatous pole). In addition, were observed low expression of caspase-1, interleukin-1β, and interleukin-18 in tuberculoid and lepromatous leprosy. The interpolar or borderline form showed immunophenotype predominantly similar to the lepromatous pole. MAIN CONCLUSIONS Our results demonstrate that the NLRP3 inf lammasome is inactive in leprosy, suggesting immune evasion of M. leprae.