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

Wenya Gao,Renjie Chang,Yuena Sun,Tianjun Xu

doi:10.3389/fimmu.2021.647202

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.

Highlights

Innate immunity and acquired immunity are important ways for the body to protect itself from pathogenic microorganisms [1]
We have explored the expression of miR-2187 and the relationship between miR-2187 and tumor necrosis factor receptor related factor 6 (TRAF6) under the stimulation of Gram-negative bacteria or Siniperca chuatsi rhabdovirus (SCRV), a typical fish RNA rhabdovirus
These results demonstrated that miR-2187 could be regulated in miiuy croaker in response to Gram-negative bacterial and SCRV infection

Summary

Introduction

Innate immunity and acquired immunity are important ways for the body to protect itself from pathogenic microorganisms [1]. Invading pathogens are effectively identified by various extracellular or intracellular pattern-recognition receptors (PRRs) which can recognize conserved signature molecular structures termed as pathogen-associated molecular patterns (PAMPs) [2]. PRRs rapidly initiate a series of immune responses by inducing the production of inflammatory cytokines, chemokines, and type I interferon (IFNs) after ligand binding [3]. PRRs are a kind of evolutionarily conserved host sensor, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors. TLRs and RLRs are the most studied receptors in the immune responses [4, 5]. TLRs are recognized as the main sensors of pathogens involved in the regulation of innate and adaptive immune system. Once TLRs recognize the molecular structure of pathogens, MicroRNA-2187 Modulates Fish Immune Response

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Conclusion