Infection and Drug Resistance (Nov 2018)
The inflammasome in leprosy skin lesions: an immunohistochemical evaluation
Abstract
Luciana Mota Silva,1 Jorge Rodrigues de Sousa,2,3 Kelly Emi Hirai,1 Leônidas Braga Dias Jr,1 Ismari Perini Furlaneto,1 Francisca Regina Oliveira Carneiro,1 Tinara Leila de Souza Aarão,1 Mirian Nacagami Sotto,4,5 Juarez Antonio Simões Quaresma1–3,5 1Center of Biological and Health Science, State University of Para, Belem, Brazil; 2Tropical Medicine Center, Federal Do Para University, Belem, Brazil; 3Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil; 4School of Medicine, Sao Paulo University, Sao Paulo, Brazil; 5Tropical Medicine Institute, Sao Paulo University, Sao Paulo, Brazil Objective: Leprosy is a chronic infectious disease presenting with a spectrum of clinical manifestations that correspond to the type of immune response that develops in the host. Factors that may be involved in this process include inflammasomes, cytosolic proteins responsible for the activation of caspase 1, IL-1β and IL-18 secretion, and induction of a type of death called pyroptosis.Patients and methods: We evaluated the expression of inflammasome markers (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 [NLRP1], nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 [NLRP3], caspase 1, IL-1β, and IL-18) by immunohistochemistry in 43 samples of skin lesions of leprosy patients from the groups indeterminate (I) leprosy (13 patients), tuberculoid (TT) leprosy (15 patients), and lepromatous leprosy (LL; 15 patients).Results: The evaluated markers were most upregulated in LL lesions, followed by lesions of TT leprosy and I leprosy. Differences were statistically significant between the I leprosy and LL leprosy forms and between the I leprosy and TT leprosy forms. Positive and significant correlations were found between IL-18 and caspase 1 in LL (r=0.7516, P=0.0012) and TT leprosy (r=0.7366, P=0.0017). In I leprosy, correlations were detected between caspase 1 and IL-1β (r=0.6412, P=0.0182), NLRP1 and IL-18 (r=0.5585, P=0.473), NLRP3 and IL-18 (r=0.6873, P=0.0094), and NLRP1 and NLRP3 (r=0.8040, P=0.0009).Conclusion: The expression of inflammasome markers in LL lesions indicates the ineffectiveness of this protein complex in controlling the infection. Caspase 1 may be involved in the pyroptotic cell death in the lepromatous form of the disease. Inflammasomes may act together in the initial phase of I leprosy; this phenomenon may influence the clinical outcome of the disease. Keywords: IL-1β, NLRP, Mycobacterium leprae, immune response, pyroptosis
