Conclusion
Higher expression levels of IFITs reduce in vitro survival of different drug-susceptible and drug-resistant mycobacteria and correlates with latent TB infection in infected individuals, hence emerging as an immuno-therapeutic target against M. tb.
Methods
We performed vector-driven overexpression and siRNA-mediated downregulation of IFITs in THP-1 cells infected with different mycobacterial species. Also, we investigated the mRNA levels of IFITs in the LTBI and active-TB cases.
Results
Overexpression of IFITs reduces CFUs by ~32% (30%-43%) [Median (IQR)] across three different mycobacterial strains, while knock-down increases CFUs by ~57% (41%-78%). Compared to IFN-γ, treatment of infected THP-1 cells with IFN-β significantly increases the expression of IFITs, while the overexpression of IFITs had higher mRNA expression of IFN-β than IFN-γ. Cytokines like IDO-1, IL-6, IL-23, and IFN- γ are observed to play key roles in mycobacterial survival upon IFITs intervention. mRNA expression levels of IFITs were higher in LTBI cases as compared to active TB.