Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells

• DOI: 10.1371/journal.ppat.1006790
• Publication Date: 2018-01-04T19:49:22Z
• Authors: Marilena P. Etna; Alessandro Siniga...; Angela Grassi; Elena Giacomini; Alessandra Romagnoli; Manuela Pardini; Martina Severa; Melania Cruciani; Fabiana Rizzo; Eleni Anastasiadou; Barbara Di Camillo; Luisa Barzon; Gian Maria Fimia; Riccardo Manganelli; Eliana M. Coccia
• Keywords: Autophagosome

Autophagy is a primordial eukaryotic pathway, which provides the immune system with multiple mechanisms for elimination of invading pathogens including Mycobacterium tuberculosis (Mtb). As consequence, Mtb has evolved different strategies to hijack autophagy process. Given crucial role human primary dendritic cells (DC) in host immunity control, we characterized Mtb-DC interplay by studying contribution cellular microRNAs (miRNAs) post-transcriptional regulation related genes. From expression profile de-regulated miRNAs obtained Mtb-infected DC, identified 7 whose was previously found be altered specimens TB patients. Among them, gene ontology analysis showed that miR-155, miR-155* and miR-146a target mRNAs significant enrichment biological processes linked autophagy. Interestingly, miR-155 significantly stimulated live virulent enriched polysome-associated RNA fraction, where actively translated reside. The putative pair interaction among E2 conjugating enzyme involved LC3-lipidation autophagosome formation-ATG3-and arose prediction analysis, confirmed both luciferase reporter assay Atg3 immunoblotting miR-155-transfected also consistent protein LC3 lipidated form reduction. Late infection, when peaked, level number puncta per cell (autophagosomes) decreased dramatically. In accordance, silencing rescued infected DC enhanced autolysosome fusion, thereby supporting unidentified as inhibitor ATG3 expression. Taken together, our findings suggest how can manipulate miRNA regulate its own survival, highlight importance develop novel therapeutic against would boost