02374nas a2200385 4500000000100000008004100001653001500042653000900057653002500066653001200091653002800103653001400131100002000145700001700165700002000182700001700202700002100219700002100240700001200261700001600273700001600289700002200305700001100327700001500338700001600353700001500369700001600384700001200400700001100412700001600423700001300439245012900452520139300581022001401974 2016 d10aType I IFN10aOASL10aMycobacterium leprae10aleprosy10aCytoplasmic DNA sensing10aAutophagy1 aToledo-Pinto TG1 aFerreira ABR1 aRibeiro-Alves M1 aRodrigues LS1 aBatista-Silva LR1 aAndrade Silva BJ1 aLemes R1 aMartinez AN1 aSandoval FG1 aAlvarado-Arnez LE1 aRosa P1 aShannon EJ1 aPessolani M1 aPinheiro R1 aAntunes SLG1 aSarno E1 aLara F1 aWilliams DL1 aMoraes M00aSTING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.3 a
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.
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