MicroRNA-2187 Modulates the NF-κB and IRF3 Pathway in Teleost Fish by Targeting TRAF6

Front Immunol. 2021 Feb 15:12:647202. doi: 10.3389/fimmu.2021.647202. eCollection 2021.

Abstract

The innate immune organs and cells detect the invasion of pathogenic microorganisms, which trigger the innate immune response. A proper immune response can protect the organisms from pathogen invasion. However, excessive immunity can destroy immune homeostasis, leading to uncontrolled inflammation or pathogen transmission. Evidence shows that the miRNA-mediated immune regulatory network in mammals has had a significant impact, but the antibacterial and antiviral responses involved in miRNAs need to be further studied in lower vertebrates. Here, we report that miR-2187 as a negative regulator playing a critical role in the antiviral and antibacterial response of miiuy croaker. We find that pathogens such as Vibrio anguillarum and Siniperca chuatsi rhabdovirus (SCRV) can up-regulate the expression of miR-2187. Elevated miR-2187 is capable of reducing the production of inflammatory factors and antiviral genes by targeting TRAF6, thereby avoiding excessive inflammatory response. Furthermore, we proved that miR-2187 modulates innate immunity through TRAF6-mediated NF-κB and IRF3 signaling pathways. The above results indicate that miR-2187 acts as an immune inhibitor involved in host antibacterial and antiviral responses, thus enriching the immune regulatory network of the interaction between host and pathogen in lower vertebrates.

Keywords: TRAF6; fish; immune response; miR-2187; negative regulation.

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Fish Diseases / genetics
  • Fish Diseases / microbiology
  • Fish Diseases / virology
  • Fish Proteins / genetics*
  • Fish Proteins / metabolism
  • Gene Expression Regulation / immunology
  • Host-Pathogen Interactions / immunology
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Interferon Regulatory Factor-3 / genetics*
  • Interferon Regulatory Factor-3 / metabolism
  • MicroRNAs / genetics*
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Perciformes / genetics*
  • Perciformes / microbiology
  • Perciformes / virology
  • Rhabdoviridae / immunology
  • Rhabdoviridae / physiology
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • TNF Receptor-Associated Factor 6 / genetics*
  • TNF Receptor-Associated Factor 6 / metabolism
  • Vibrio / immunology
  • Vibrio / physiology

Substances

  • Cytokines
  • Fish Proteins
  • Interferon Regulatory Factor-3
  • MicroRNAs
  • NF-kappa B
  • TNF Receptor-Associated Factor 6

Supplementary concepts

  • Vibrio anguillarum