Autophagy Is an Innate Mechanism Associated with Leprosy Polarization

• DOI: 10.1371/journal.ppat.1006103
• Publication Date: 2017-01-09T23:01:00Z
• Authors: Bruno Jorge de An...; Mayara Garcia de ...; Priscila Ribeiro ...; Helen Ferreira; José Augusto da C...; Suzana Côrte-Real; Gilberto Marcelo ...; Patricia Sammarco...; Mario Fabri; Euzenir Nunes Sarno; Roberta Olmo Pinh...
• Keywords: BECN1; Mycobacterium leprae; Sequestosome 1

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of host. Levels IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. primes macrophages for inflammatory activation and induces autophagy antimicrobial mechanism. The involvement against Mycobacterium leprae remains unexplored. Here, we demonstrated by autophagic assays LC3-positive autophagosomes were predominantly observed T-lep L-lep lesions skin-derived macrophages. Accumulation receptors SQSTM1/p62 NBR1, expression lysosomal peptides colocalization analysis autolysosomes revealed an impairment flux cells, which was restored or rapamycin treatment. Autophagy PCR array gene-expression upregulation genes (BECN1, GPSM3, ATG14, APOL1, TPR) cells. Furthermore, (TPR, GFI1B GNAI3) as well LC3 levels cells patients developed type 1 reaction (T1R) episodes, acute condition associated increased levels. Finally, BCL2 could be responsible blockage BECN1-mediated autophagy. In addition, vitro studies dead, but not live M. can induce primary lineage human monocytes, mycobacteria reduce triggered dead mycobacteria, suggesting hamper machinery escape Together, these results indicate important innate mechanism control skin