OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion.

The 2',5' (OASs) are known as mediators of the antiviral response system through activation of the RNA cleavage pathway. Interestingly, we observe OAS1, OAS2 and OAS3 upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however their biological role during bacterial infection has not yet been elucidated. We observed that the expression of these genes was associated with pathogenicity and virulence of mycobacteria as infection with Mycobacterium bovis BCG failed to significantly induce OAS expression. Further, we observed that after silencing of these genes, M. tb CFU counts increased significantly 96h post-infection in comparison to the respective controls. Luminex revealed that OAS silencing significantly decreased IL-1β, TNF-α and MCP-1 and had no effect of IL-10 secretion. We show for the first time that OAS1, 2 and 3 restrict intracellular pathogenic mycobacterial replication and enhance pro-inflammatory cytokine secretion.