OAS1, 2, and 3: Significance During Active Tuberculosis?

Abstract

Evidence to-date points to a detrimental role of the type I IFNs during tuberculosis. The mechanisms underpinning the IFNαβ-mediated exacerbation of the disease is unclear. The 2'-5'-oligoadenylate synthetases (OAS), namely OAS1, OAS2 and OAS3 are part of the interferon-induced genes which until now have been synonymous with an anti-viral function. Blood transcriptome profiling has continuously observed their upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however the role of the OASs and the effect that their expression has on the pathogenesis and persistence of TB is unknown. Evidence suggests that the OASs exhibit other cellular functions which include the induction of apoptosis, enhancement of IFNαβ signalling, immune cell receptor modulation and autophagy. We propose that i) during the late stages of disease, sustained RNaseL expression through OAS activation enhances type I IFN signalling and, ii) that they may exhibit immune-modulatory capabilities.