Modulation of fish immune response by interferon regulatory factor 4 in redlip mullet (Liza haematocheilus): Delineation through expression profiling, antiviral assay, and macrophage polarization analysis

• Published in: Developmental and comparative immunology 2022-05, Vol.130, p.104356-104356, Article 104356
• Main Authors: Harasgama, J.C., Kasthuriarachchi, T.D.W., Sirisena, D.M.K.P., Kwon, Hyukjae, Lee, Seongdo, Wan, Qiang, Lee, Jehee
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Antiviral; Antiviral Agents; Blood cells; Deoxyribonucleic acid; DNA; Fish Diseases; Fish Proteins - metabolism; Fishes - genetics; Gene Expression Profiling; Gene Expression Regulation; Hemorrhage; Hemorrhagic septicemia; Homology; Immune response; Immune system; Immunity, Innate - genetics; Immunomodulation; Infections; Interferon; Interferon regulatory factor; Interferon regulatory factor 4; Interferon regulatory factor 4 (IRF4); Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Intestine; Kidneys; Macrophage polarization; Macrophages; Mice; Microbial infection; Microorganisms; Phylogeny; Polarization; RAW 264.7 Cells; Redlip mullet; Smegmamorpha; Spleen; Structure-function relationships; Vertebrates; Viruses
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2022.104356

Interferon regulatory factor 4 (IRF4) is a crucial member of IRF family, which acts as an imperative transcription factor in the development and maturation of multiple lineages of blood cells and also plays a pivotal role in host defense against microbial infections. In the present study, we aimed to investigate the detailed structural and functional aspects of a redlip mullet IRF4 homolog (LhIRF4). The LhIRF4 open reading frame consists of 1347 base pairs encoding 449 amino acids, with the DNA-binding domain sharing significant homology with that of other vertebrate IRF4 homologs. The highest transcription levels of LhIRF4 were observed in the mullet intestine and spleen under normal physiological conditions. Furthermore, a time-dependent upregulation of LhIRF4 transcription was observed in the spleen and head kidney tissues upon pathogenic challenges. When overexpressed in mullet cells, LhIRF4 was localized to the nucleus and significantly stimulated the transcription of several host antiviral genes. Moreover, the overexpression of LhIRF4 strongly inhibited the replication of viral hemorrhagic septicemia virus (VHSV) in vitro. The function of LhIRF4 in regulation of macrophage M2 polarization has also been evidently demonstrated in RAW 264.7 cells. Taken together, our findings indicate the profound role of LhIRF4 in modulating immune responses against microbial infections in redlip mullet. •Interferon regulatory factor 4 of Liza haematocheilus was characterized (LhIRF4).•The highest transcription of LhIRF4 was observed in the fish intestine.•Transcription of LhIRF4 was modulated upon immune challenges.•LhIRF4 significantly reduced the copy number of viral hemorrhagic septicemia virus (VHSV).•LhIRF4 could polarize macrophages into M2 stage.