MicroRNA-31 mediated by interferon regulatory factor 7 signaling facilitates control of Mycobacterium tuberculosis infection

Int J Med Microbiol. 2022 Oct;312(7):151569. doi: 10.1016/j.ijmm.2022.151569. Epub 2022 Sep 27.

Abstract

Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection.

Keywords: Mycobacterium tuberculosis; Tuberculosis; miRNA-31.

MeSH terms

  • B7-H1 Antigen
  • Humans
  • Interferon Regulatory Factor-7 / genetics
  • MicroRNAs* / genetics
  • Mycobacterium tuberculosis*
  • Programmed Cell Death 1 Receptor
  • Tuberculosis* / microbiology

Substances

  • B7-H1 Antigen
  • Interferon Regulatory Factor-7
  • Programmed Cell Death 1 Receptor
  • MicroRNAs
  • MIRN31 microRNA, human