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 inflammatory and immune responses. More recently, the inflammasome has assumed a relevant role in the inflammatory response against microbiological agents. However, the involvement of inflammasome in leprosy remains poorly understood.

Objectives: The aim is to associate biomarkers of inflammasome with the different immunopathological forms of leprosy.

Methods: We performed an observational, cross-sectional, and comparative study of the immunophenotypic expression of inflammasome-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 inflammatory infiltrate of skin biopsies were evaluated.

Findings: Strong expression of NLRP3 and inflammatory 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 inflammasome is inactive in leprosy, suggesting immune evasion of M. leprae.

Fig. 1:. expression of NLRP3 in the immunopathological forms of leprosy. (A) polar tuberculoid (TT)/borderline tuberculoid (BT)-group showing mild NLRP3 staining in granuloma macrophages (400x magnification; Bar: 50 µM); (B) lepromatous leprosy (LL)/ borderline lepromatous (BL) group showing intense and diffuse staining for NLRP3 in macrophages (400x magnification; Bar: 50 µM).

Fig. 2:. expression of caspases-4/5 in the immunopathological forms of leprosy. (A) polar tuberculoid (TT)/ borderline tuberculoid (BT)-group showing slight staining for caspases-4/5 in inflammatory cells (400x magnification; Bar: 50 µM); (B) borderline borderline (BB)-group presenting intense staining for caspases-4/5 in inflammatory cells (400x magnification; Bar: 50 µM).