Skip to main content

ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1536446

IFIT2-induced transcriptomic changes in Mycobacterium tuberculosis infected macrophages

Provisionally accepted
Ewura-Esi Manful Ewura-Esi Manful 1*Bienyameen Baker Bienyameen Baker 2*Ray-Dean Pietersen Ray-Dean Pietersen 2
  • 1 The Pennsylvania State University (PSU), University Park, United States
  • 2 DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

The final, formatted version of the article will be published soon.

    Interferon-induced protein with tetratricopeptide repeat 2 (IFIT2) is known for its antiviral activity and has recently been implicated in the defence against Mycobacterium tuberculosis (M. tb). This study employed global transcriptomics to investigate the downstream effects of IFIT2 induction in THP-1 macrophages infected with R179 M. tb, aiming to elucidate its role and downstream contributing factors that aid it in intracellular M. tb killing. Using a vector-based overexpression approach, IFIT2 expression was induced in THP-1 cells infected with R179 M. tb, followed by RNA extraction 12 hours post-infection and AmpliSeq-based targeted transcriptome sequencing. Bioinformatics analysis identified 282 differentially expressed genes (DEGs), of which 189 were upregulated and 90 were downregulated (FDR <0.05). Filtering for highly significant DEGs (|log2(fold change) | > 1.5) yielded 70 genes, predominantly upregulated, with functional enrichment in pathways such as defence response to viruses and cytokine-mediated signalling. Signalling pathway impact analysis highlighted pathway activation and inhibition of the tuberculosis (TB) pathway. RT-qPCR validation confirmed the upregulation of selected DEGs (ISG15, CMPK2, RSAD2, IFI44L, IFI44), corroborating the AmpliSeq data. This study provides comprehensive insights into the transcriptomic profile induced by IFIT2 in TB, revealing critical downstream contributors and pathways that underpin IFIT2's ability to combat M. tb infection.

    Keywords: IFIT2, Macrophages, Tuberculosis, Transcriptomics, Gene Expression, host-pathogen interaction

    Received: 28 Nov 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Manful, Baker and Pietersen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ewura-Esi Manful, The Pennsylvania State University (PSU), University Park, United States
    Bienyameen Baker, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.