Universität zu Köln

de Andrade Silva, Bruno Jorge, de Mattos Barbosa, Mayara Garcia, Andrade, Priscila Ribeiro, Ferreira, Helen, da Costa Nery, Jose Augusto, Corte-Real, Suzana, Sperandio da Silva, Gilberto Marcelo, Rosa, Patricia Sammarco, Fabri, Mario, Sarno, Euzenir Nunes and Pinheiro, Roberta Olmo (2017). Autophagy Is an Innate Mechanism Associated with Leprosy Polarization. PLoS Pathog., 13 (1). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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Abstract

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-gamma are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-gamma 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-gamma 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-gamma 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code de Andrade Silva, Bruno Jorge UNSPECIFIED UNSPECIFIED UNSPECIFIED de Mattos Barbosa, Mayara Garcia UNSPECIFIED UNSPECIFIED UNSPECIFIED Andrade, Priscila Ribeiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferreira, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED da Costa Nery, Jose Augusto UNSPECIFIED UNSPECIFIED UNSPECIFIED Corte-Real, Suzana UNSPECIFIED UNSPECIFIED UNSPECIFIED Sperandio da Silva, Gilberto Marcelo UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosa, Patricia Sammarco UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabri, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Sarno, Euzenir Nunes UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinheiro, Roberta Olmo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-246452
DOI:	10.1371/journal.ppat.1006103
Journal or Publication Title:	PLoS Pathog.
Volume:	13
Number:	1
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSES; EXPRESSION; INDUCTION; PROFILES; SURVIVAL; ACTIVATION; PATHWAYS; DEFENSE; TARGETS Multiple languages Microbiology; Parasitology; Virology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24645