Dados do Trabalho

Título

Inflammasome activation in the leprosy neuropathy

Introdução

Neural damage during leprosy may occur by Mycobacterium leprae, that has tropism for Schwann cells (SC), or by inflammatory cytokines, produced mainly during leprosy reactions that are responsible for incapacities and represent the major cause of permanent neuropathy. This scenario becomes more important when we consider patients who do not develop skin lesions, with strictly neural symptoms, knows as Pure Neural Leprosy (PNL). Our previous study demonstrated that the type 1 reaction outcome is associated with an impairment in autophagy process in skin lesion cells associated with the increased expression of inflammasome proteins. Furthermore, an increase in serum levels of IL-1β, has been demonstrated in patients with leprosy neuropathy.

Objetivo (s)

The aim of our study was to investigate the involvement of inflammasome during leprosy neuropathy.

Material e Métodos

For ex vivo experiments, RNAseq, qRT-PCR and immunofluorescence in nerve fragments were performed, and for in vitro experiments, microarray of human primary SC and ELISA of supernatants of the ST8814 human SC lineage were performed.

Resultados e Conclusão

The transcriptomic analysis of primary SC demonstrated that M. leprae infection triggers a positive regulation of inflammasome genes like NLRP1 and PYCARD after 24h. Likewise, analysis of RNAseq in nerve fragments from PNL patients demonstrated that inflammasome pathway is enriched when compared to non-leprosy neuropathy patients. qRT-PCR analysis confirmed this observation, since there were increased expressions of both IL1B and IL18 in nerve fragments from PNL patients in comparison to healthy donors. In addition, the immunofluorescence microscopy demonstrated the expression of ASC in the perineurium from PNL patients, suggesting that the inflammasome pathway could be involved in the leprosy neuropathy. Both live and dead M. leprae, as well as differents mycobacterial components, such as DNA, soluble fraction of M. leprae, membrane fraction of M. leprae and the core of M. leprae cell-wall with or without LPS were able to increase IL-1β levels in supernatants from the ST88-14 after 18h, as revealed by ELISA. Moreover, live and dead M. leprae increased IL-18 levels in supernatants from ST88-14 in relation to non-stimulated cultures after 18h. Our results suggest that M. leprae, as well as differents mycobacterial antigens may activate the inflammasome pathway in SC and thus could be involved in the pathogenesis of leprosy neuropathy.

Palavras-chave

Inflammasome, neuropathy, leprosy

Agradecimentos

CNPq, FAPERJ, CAPES, INOVA-Fiocruz