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.

Reduction of host cell mitochondrial activity as Mycobacterium leprae’s strategy to evade host innate immunity

“…The inflammasome orchestrates these events before pro-inflammatory cell death, also known as pyroptosis. 77,78 It is interesting to note that despite HIF-1α stabilization, 75 neither inflammasome activation 79 nor programmed cell death [80][81][82] are observed during M leprae infection. Perhaps the avoidance of inflammasome activation is one of the multiple benefits accrued by this pathogen in promoting a mitochondrial shutdown.…”

A Study of NLRC4 in Patients with Leprosy

“…The significant increase of NLRC4 in LL compared to the control group is consistent with a study by Mendes et al . [ 19 ] in which immunophenotypic expression of inflammasome-associated proteins in immunopathological forms of leprosy of 99 skin lesion samples was evaluated by immunohistochemistry, and it was determined that lepromatous leprosy exhibits a strong expression of NLRP3, an NLR component similar to NLRC4.…”

“…Mendes et al . [ 19 ] reported that the high expression of NLRP3 in samples of MB forms could be attributable to the high concentration of M. leprae bacilli in these tissues and that the absence or small number of viable bacilli present in tuberculoid pole lesions was insufficient to activate the inflammasome.…”

Interaction of Mycobacteria With Host Cell Inflammasomes

“…Moreover, they also found that by inhibiting NF-κB (signal 1) and P2X7R (signal 2) they can alter the secretion of IL-1β and IL-18 and thereby regulate the NLRP3 inflammasome pathway in microglia during Mtb infection ( 15 ) ( Table 1 ). Interestingly, irrespective of the overexpression of NLRP3 and inflammatory caspases-4/5 detected in the lepromatous pole, low expression of caspase-1, IL-1β, and IL-18 were observed in leprosy and therefore these results indicate that NLRP3 inflammasome does not actively contribute to the innate immune response in leprosy, suggesting immune evasion of M. leprae ( 136 ).…”