AUTHOR=Madhvi Abhilasha , Mishra Hridesh , Chegou Novel N. , Baker Bienyameen 

TITLE=Increased Interferon-Induced Protein With Tetracopeptides (IFITs) Reduces Mycobacterial Growth

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.828439

DOI=10.3389/fcimb.2022.828439

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>The host immune response towards <italic>Mycobacterium tuberculosis</italic> (<italic>M. tb</italic>) is known to vary with the virulence of mycobacterial species. While the majority of <italic>M. tb-</italic>exposed individuals develop latent TB infection (LTBI), a small proportion develops active TB disease. The milieu of understudied immune factors is believed to play an important role against host immune response towards mycobacteria. Here, we investigate the role of antiviral factors of the interferon-induced proteins with tetracopeptides (<italic>IFITs</italic>) family, which, in our previous research, have shown to be upregulated in response to pathogenic <italic>M. tb</italic>, but as yet have no established role in host response to bacterial infections. </p></sec><sec><title>Methods</title><p>We performed vector-driven overexpression and siRNA-mediated downregulation of <italic>IFITs</italic> in THP-1 cells infected with different mycobacterial species. Also, we investigated the mRNA levels of <italic>IFITs</italic> in the LTBI and active-TB cases.</p></sec><sec><title>Results</title><p>Overexpression of <italic>IFITs</italic> 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 <italic>IFITs</italic>, while the overexpression of <italic>IFITs</italic> 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 <italic>IFITs</italic> intervention. mRNA expression levels of <italic>IFITs</italic> were higher in LTBI cases as compared to active TB.</p></sec><sec><title>Conclusion</title><p>Higher expression levels of <italic>IFITs</italic> reduce <italic>in vitro</italic> 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 <italic>M. tb</italic>.</p></sec>