Type I IFNs expression levels a prognostic marker to monitor response to chemotherapy among tuberculosis patients
Vibha Taneja1,2,4 Priya Kalra2, Manish Goel3, Gopi Chand Khilnani3, Vikram Saini2, GBKS Prasad4 , Umesh D Gupta1 Jaya Sivaswami Tyagi2 and Hanumanthappa Krishna Prasad2
1 National JALMA Institute of Leprosy and other Mycobacterial Diseases, Tajganj, Agra, India;2 Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India; 3 Department of Pulmonary and sleep disorders, All India Institute of Medical Sciences, New Delhi 110029, India; 4 Department of Biochemistry, Jiwaji University, Gwalior, Madhya Pradesh, India
Mycobacterium tuberculosis (M.tb) infection stimulates the release of interferons (IFNs). IFNs mediate multiple functions that influence immune response. Accordingly, the expression levels of Type I (α, β) and II (γ) 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. IFN-α mRNA expression levels predominated compared to IFN-γ and IFN-β among untreated TB patients. IFN-α transcripts were ~3.5 folds higher in TB patients compared to HHC, (p<0.0001). High expression of IFN-α was seen among 46% (56/ 123) TB patients and 26%, (22/86) of HHCs. The expression levels of IFN-α correlated with that of IFN transcriptional release factor 7 (IRF) (p<0.0001); whereas an inverse relationship exists between PGE2 and IFN-α expression levels; high IFN-α expressers were associated with low levels of PGE2 and vice-versa (Spearman’s rho = -0.563; p<0.0001). In-vitro, the anti-mycobacterial activity of IFN-γ was compromised in the presence of IFN-α, but not by IFN-β. The expression of IFN-α and β diminished or is absent, among successfully treated TB patients. These observations suggest the utility of assessing Type I IFNs expression levels as a prognostic marker to monitor patient response to chemotherapy because changes in Type I IFNs expression are expected to precede the clearance and /reduction in bacterial load.