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

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.

More information

Type
Journal Article
Author
Toledo-Pinto TG
Ferreira ABR
Ribeiro-Alves M
Rodrigues LS
Batista-Silva LR
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
Year of Publication
2016
Journal
The Journal of infectious diseases
Language
eng
ISSN Number
1537-6613
DOI
10.1093/infdis/jiw144
Alternate Journal
J. Infect. Dis.
Publication Language
eng