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Autophagy impairment is associated with increased inflammasome activation and reversal reaction development in multibacillary leprosy.

Abstract

Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of multibacillary leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of and . The autophagy impairment in T1R group was associated with increased expression of , caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in -stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in multibacillary leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.

More information

Type
Journal Article
Author
Mattos Barbosa MG
Andrade Silva BJ
Assis TQ
Silva Prata RB
Ferreira H
Andrade PR
Paixão de Oliveira JA
Sperandio da Silva GM
Costa Nery JA
Sarno EN
Pinheiro RO
Year of Publication
2018
Journal
Frontiers in immunology
Volume
9
Number of Pages
1223
Language
eng
ISSN Number
1664-3224
DOI
10.3389/fimmu.2018.01223
Alternate Journal
Front Immunol
Publication Language
eng