Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/19677
Title: Autophagy Is an Innate Mechanism Associated with Leprosy Polarization
Authors: Silva, Bruno Jorge de Andrade
Barbosa, Mayara Garcia de Mattos
Andrade, Priscila Ribeiro
Ferreira, Helen
Nery, José Augusto da Costa
Côrte-Real, Suzana
Silva, Gilberto Marcelo Sperandio da
Rosa, Patricia Sammarco
Fabri, Mario
Sarno, Euzenir Nunes
Pinheiro, Roberta Olmo
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Instituto Lauro de Souza Lima. Laboratório Casa do Animal. São Paulo, SP, Brasil.
University of Cologne. Department of Dermatology. Cologne, Germany / University of Cologne. Center for Molecular Medicine. Cologne, Germany.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.
Abstract: Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.
Keywords: Leprosy
Autophagy
innate mechanism
keywords: Hanseníase
Autofagia
Mecanismo inato
Issue Date: 2017
Publisher: Public Library of Science
Citation: SILVA, Bruno Jorge de Andrade; et al. Autophagy Is an Innate Mechanism Associated with Leprosy Polarization. PLoS Pathog, v.13, n.1, e1006103, 29p, Jan. 2017.
DOI: 10.1371/journal.ppat.1006103
ISSN: 1553-7366
Copyright: open access
Appears in Collections:INI - Artigos de Periódicos
IOC - Artigos de Periódicos

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