Impact and prognosis of the expression of IFN-alpha among tuberculosis patients

Mycobacterium tuberculosis (M.tb) infection stimulates the release of cytokines, including interferons (IFNs). IFNs are initiators, regulators, and effectors of innate and adaptive immunity. Accordingly, the expression levels of Type I (alpha, beta) and II (gamma) IFNs, among untreated tuberculosis (TB) patients and household contacts (HHC) clinically free of TB was assessed. A total of 264 individuals (TB patients-123; HHC-86; laboratory volunteers-55; Treated TB patients-36) were enrolled for this study. IFN-alpha mRNA expression levels predominated compared to IFN-gamma and IFN-beta among untreated TB patients. IFN-alpha transcripts were similar to 3.5 folds higher in TB patients compared to HHC, (p<0.0001). High expression of IFN-alpha was seen among 46% (56/123) of the TB patients and 26%, (22/86) of HHCs. The expression levels of IFN-alpha correlated with that of IFN transcriptional release factor 7 (IRF) (p<0.0001). In contrast, an inverse relationship exists between PGE2 and IFN-alpha expression levels; high IFN-alpha expressers were associated with low levels of PGE2 and vice-versa (Spearman's rho = -0.563; p<0.0001). In-vitro, IFN-alpha failed to restrict the replication of intracellular M.tb. The anti-mycobacterial activity of IFN-gamma was compromised in the presence of IFN-alpha, but not by IFN-beta. The expression of IFN-alpha and beta diminished or is absent, among successfully treated TB patients. These observations suggest the utility of assessment of Type I IFNs expression levels as a prognostic marker to monitor tuberculosis patient response to chemotherapy because changes in Type I IFNs expression are expected to precede the clearance and /reduction in bacterial load.