STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.

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TitleSTING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.
Publication TypeJournal Article
Authorsde Toledo-Pinto TG, Ferreira ABR, Ribeiro-Alves M, Rodrigues LS, Batista-Silva LR, de Silva BJA, Lemes RMR, Martínez AN, Sandoval FG, Alvarado-Arnez LE, Rosa PS, Shannon EJ, Pessolani MCV, Pinheiro RO, Antunes SLG, Sarno EN, Lara FA, Williams DL, Ozório Moraes M
Abbrev. JournalJ. Infect. Dis.
JournalThe Journal of infectious diseases
Year of Publication2016
Publication Languageeng
KeywordsAutophagy, Cytoplasmic DNA sensing, Leprosy, Mycobacterium leprae, OASL, Type I IFN
Abstract

Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen.

PubMed URL

http://www.ncbi.nlm.nih.gov/pubmed/27190175?dopt=Abstract

DOI10.1093/infdis/jiw144