IRF9 as a negative regulator involved in TRIF-mediated NF-κB pathway in a teleost fish, Miichthys miiuy

Zhao, Xueyan; Chu, Qing; Cui, Junxia; Huo, Ruixuan; Xu, Tianjun

doi:10.1016/j.molimm.2017.02.009

Cited by 40 publications

(15 citation statements)

References 33 publications

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“…Typically, IRF9 is considered a positive regulator of gene transcription. However, our findings are consistent with recent reports documenting the role of IRF9 in the negative regulation of the TRIF/NF-κB transcriptional response 31 or the expression of SIRT1 in acute myeloid leukemia cells 32 . The molecular mechanism underlying gene regulation by IRF9 without association with either STAT1 or STAT2 remain to be elucidated.…”

Section: Discussionsupporting

confidence: 93%

IFNβ and TNFα cooperate to induce a STAT1-independent antiviral and immunoregulatory program via non-canonical STAT2 and IRF9 pathways

Mariani

Dasmeh

Fortin

et al. 2018

Preprint

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IFNβ typically induces an antiviral and immunoregulatory transcriptional program through the activation of ISGF3 (STAT1, STAT2 and IRF9) transcriptional complexes. The response to IFNβ is context-dependent and is prone to crosstalk with other cytokines, such as TNFα IFNβ and TNFα synergize to drive a specific delayed transcriptional program. Previous observation led to the hypothesis that an alternative STAT1-independent pathway involving STAT2 and IRF9 might be involved in gene induction by the combination of IFNβ and TNFα. Using genome wide transcriptional profiling by RNASeq, we found that the costimulation with IFNβ and TNFα induces a broad antiviral and immunoregulatory transcriptional program independently of STAT1. Additionally, STAT2 and IRF9 are involved in the regulation of only a subset of these STAT1-independent genes. Consistent with the growing literature, STAT2 and IRF9 act in concert to regulate a subgroup of these genes. Unexpectedly, STAT2 and IRF9 were also engaged in specific independent pathways to regulate distinct sets of IFNβ and TNFα-induced genes. Altogether these observations highlight the existence of distinct previously unrecognized non-canonical STAT1-independent, but STAT2 and/or IRF9-dependent pathways in the establishment of a delayed antiviral and immunoregulatory transcriptional program in conditions where elevated levels of both IFNβ and TNFα are present.

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Section: Discussionsupporting

confidence: 93%

IFNβ and TNFα cooperate to induce a STAT1-independent antiviral and immunoregulatory program via non-canonical STAT2 and IRF9 pathways

Mariani

Dasmeh

Fortin

et al. 2018

Preprint

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“…Dual luciferase reporter assays showed that the overexpression of Irf9 in 293 T cells has no effect on the Trif or Myd88‐mediated NF‐κB pathway. Overexpression of M. miiuy Irf9 could not activate NF‐κB (Yang et al, ), but other reports have shown that this protein is a negative regulator in the Trif‐mediated NF‐κB pathway (Zhao et al, ). Unfortunately, to our knowledge, there are no studies on the regulatory role of Irf9 in the NF‐κB pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The diverse roles of the protein encoded by the mammalian IRF9 gene have been well studied. Studies on this gene have been reported in several fish species, including zebrafish Danio rerio (Hamilton 1822) (Shi et al, ), grass carp Ctenopharyngodon idella (Valenciennes 1844) (Liao et al, ), crucian carp Carassius auratus (Linnaeus 1758) (Shi et al, ), Atlantic salmon Salmo salar L. 1758 (Sobhkhez et al, ), half‐smooth tongue sole Cynoglossus semilaevis Günther 1873 (Zhang et al, ), blunt snout bream Megalobrama amblycephala Yih 1955 (Zhan et al, ), large yellow croaker Larimichthys crocea (Richardson 1846) (Tang et al, ), puffer fish Dichotomyctere nigroviridis (Marion de Procé 1822) (Cheng et al, ), Japanese flounder Paralichthys olivaceus (Temminck & Schlegel 1846) (Hu et al, ) and miiuy croaker Miichthys miiuy (Basilewsky 1855) (Yang et al, ; Zhao et al, ). Most of the studies focused on the functional role of Irf9 in antiviral and antibacterial responses and the results showed that Irf9 can be induced by polyinosinic‐polycytidylic acid (poly I:C), virus or bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…In C. auratus and T. nigroviridis , Irf9 overexpression increased the transcription of Isg (Cheng et al, ; Shi et al, ). A recent report showed that fish Irf9 functions as a negative regulator in the TIR‐domain‐containing adapterinducing interferon‐β (Trif)‐mediated nuclear factor kappa‐light chain‐enhancer of activated B cells (NF‐κB) signalling pathway (Zhao et al, ). All these results demonstrate the critical role of IRF9 in the antimicrobial immune response.…”

Section: Introductionmentioning

confidence: 99%

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Molecular characterization and functional analysis of interferon regulatory factor 9 (irf9) in common carp Cyprinus carpio: a pivotal molecule in the Ifn response against pathogens

Zhu

Shan

et al. 2019

Journal of Fish Biology

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In the present study, interferon (IFN) regulatory factor (IRF) 9 gene (irf9) was identified and characterized in common carp Cyprinus carpio. The predicted protein sequence of Irf9 contains a DNA binding domain (DBD) that possess five tryptophans, an IRF association domain (IAD) and two nuclear localisation signals (NLS). Alignment of Irf9 of C. carpio with the corresponding Irf9 proteins of other species showed that the DBD is more highly conserved than the IAD. The putative Irf9 protein sequence of C. carpio shares higher identities with teleosts (53.8–82.3%) and lower identities with mammals (30.2–31.0%). Phylogenetic studies of the putative amino‐acid sequence of IRF9 based on the neighbour‐joining method showed that Irf9 of C. carpio has the closest relationship with the grass carp Ctenopharyngodon idella. Tissue distribution analysis showed that irf9 transcripts were detectable in all examined tissues with the highest expression in the skin and the lowest expression in the head kidney. Poly I:C and Aeromonas hydrophila stimulation up‐regulated irf9 expression in the spleen, head kidney, foregut and hindgut at different time intervals. In addition, irf9 was induced by Poly I:C and lipopolysaccharides (LPS) in vitro. These results indicate that Irf9 participates in antiviral and antibacterial immunity. Transfection of irf9 up‐regulated the expression of cytokines, including type I IFN, protein kinase R (PKR), interferon‐stimulated gene (ISG)15 and tumour necrosis factor (TNF)α in epithelioma papulosum cyprini cells (EPC) upon poly I:C and LPS stimulation. A dual‐luciferase reporter assay revealed that Irf9 has no effect on NF‐κB activation. The present study on Irf9 provides new insights into the IFN system of C. carpio and a valuable experimental platform for future studies on the immune system of fish.

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“…Miiuy croaker, as a member of the Sciaenidae family, is an economically important fish. The study of this species has been conducted in depth from the transcriptome (26) and whole genome (27) to immune genes (28,29), which makes the miiuy croaker an excellent model for studying the immune response of fish. The underlying mechanisms of some molecules in the regulation of immune response have been studied in this species.…”

Section: Discussionmentioning

confidence: 99%

The inducible microRNA-203 in fish represses the inflammatory responses to Gram-negative bacteria by targeting IL-1 receptor-associated kinase 4

Chu

Cui

et al. 2018

Journal of Biological Chemistry

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Innate immune responses are the first defense against pathogenic invaders. Activation and termination of these immune responses are regulated by several mechanisms. MicroRNAs (miRNAs), a group of small non-coding RNAs, have been implicated in the regulation of a spectrum of both physiological and pathological conditions, including immune responses. Although the immune regulatory miRNA networks in higher vertebrates have been well described, regulation of these responses in fish species is poorly understood. In the present study, we investigated the role of the miRNA miR-203 involved in inflammatory responses in miiuy croaker (). We found that the Gram-negative bacterium and lipopolysaccharide significantly up-regulated host miR-203 expression. The increased miR-203 expression suppressed the production of inflammatory cytokines and thereby prevented mounting of a full immune response. Mechanistically, we identified and validated IL-1 receptor-associated kinase 4 () as a target of miR-203. We observed that miR-203 post-transcriptionally controls IRAK4 expression and thereby inhibits the activation of nuclear factor κB (NF-κB) signaling. In summary, our findings reveal that miR-203 in fish is a critical suppressor of innate immune responses to bacterial infection by suppressing a feedback to IRAK4-NF-κB-mediated signaling.

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IRF9 as a negative regulator involved in TRIF-mediated NF-κB pathway in a teleost fish, Miichthys miiuy

Cited by 40 publications

References 33 publications

IFNβ and TNFα cooperate to induce a STAT1-independent antiviral and immunoregulatory program via non-canonical STAT2 and IRF9 pathways

IFNβ and TNFα cooperate to induce a STAT1-independent antiviral and immunoregulatory program via non-canonical STAT2 and IRF9 pathways

Molecular characterization and functional analysis of interferon regulatory factor 9 (irf9) in common carp Cyprinus carpio: a pivotal molecule in the Ifn response against pathogens

The inducible microRNA-203 in fish represses the inflammatory responses to Gram-negative bacteria by targeting IL-1 receptor-associated kinase 4

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