scholarly journals Identification and Functional Analysis of A Non-Mammalian IRF10 in Common Carp (Cyprinus Carpio. L) in The Antiviral and Antibacterial Immune Response

2020 ◽  
Author(s):  
Yaoyao Zhu ◽  
Shijuan Shan ◽  
Huaping Zhao ◽  
Rongrong Liu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Head Kidney ◽  
Poly I:C ◽  
Type I ◽  
Innate Immune Responses ◽  
Regulatory Factors ◽  
Polycytidylic Acid ◽  
Transcriptional Regulatory ◽  
Localization Signal

Abstract Background: Interferon (IFN) regulatory factors (IRFs), as the transcriptional regulatory factors play important roles in regulating the expression of type I IFN and IFN-stimulated genes (ISGs) in innate immune responses, as well as participate in cell growth, development and regulating the oncogenesis.Results: In the present study, the cDNA sequence of IRF10 was characterized in common carp (Cyprinus carpio L.) (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7-89.2% identities to teleost IRF10 and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had a closer relationship with the IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts was detectable in all examined tissues, with the highest expression in the gonad and the lowest expression level in the head kidney. The CcIRF10 expression was up-regulated in the spleen, head kidney, foregut and hindgut upon polyinosinic: polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation, and also induced by poly I:C, LPS and PGN in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expressions of IFN-related genes, PKR and ISG5.Conclusions: These results indicated that CcIRF10 participated in the antiviral and antibacterial immunity, and negatively regulated the IFN response, which provided new insights into the IFN system of C. carpio.

scholarly journals Identification of an IRF10 gene in common carp (Cyprinus carpio L.) and analysis of its function in the antiviral and antibacterial immune response

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaoyao Zhu ◽  
Shijuan Shan ◽  
Huaping Zhao ◽  
Rongrong Liu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Head Kidney ◽  
Ctenopharyngodon Idella ◽  
Poly I:C ◽  
Type I ◽  
Regulatory Factors ◽  
Polyinosinic:Polycytidylic Acid ◽  
Transcriptional Regulatory ◽  
Localization Signal

Abstract Background Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN- stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. Results In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7–89.2% identity with other teleost IRF10s and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had the closest relationship with IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts were detectable in all examined tissues, with the highest expression in the gonad and the lowest expression in the head kidney. CcIRF10 expression was upregulated in the spleen, head kidney, foregut and hindgut upon polyinosinic:polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation and induced by poly I:C, lipopolysaccharide (LPS) and peptidoglycan (PGN) in peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expression of the IFN and IFN-stimulated genes PKR and ISG15. Conclusions These results indicate that CcIRF10 participates in antiviral and antibacterial immunity and negatively regulates the IFN response, which provides new insights into the IFN system of C. carpio.

scholarly journals Identification of an IRF10 gene in common carp (Cyprinus carpio L.) and analysis of its function in the antiviral and antibacterial immune response

2020 ◽  
Author(s):  
Yaoyao Zhu ◽  
Shijuan Shan ◽  
Huaping Zhao ◽  
Rongrong Liu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Head Kidney ◽  
Ctenopharyngodon Idella ◽  
Poly I:C ◽  
Type I ◽  
Regulatory Factors ◽  
Common Carp Cyprinus Carpio ◽  
Transcriptional Regulatory ◽  
Carp Cyprinus Carpio

Abstract Background: Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. Results: In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7-89.2% identity with other teleost IRF10s and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had the closest relationship with IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts were detectable in all examined tissues, with the highest expression in the gonad and the lowest expression in the head kidney. CcIRF10 expression was upregulated in the spleen, head kidney, foregut and hindgut upon polyinosinic:polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation and induced by poly I:C, lipopolysaccharide (LPS) and peptidoglycan (PGN) in peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expression of the IFN and IFN stimulated genes PKR and ISG15. Conclusions: These results indicate that CcIRF10 participates in antiviral and antibacterial immunity and negatively regulates the IFN response, which provides new insights into the IFN system of C. carpio.

scholarly journals Identification and functional characterization of a fish-specific tlr19 in common carp (Cyprinus carpio L.) that recruits TRIF as an adaptor and induces ifn expression during the immune response

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Shijuan Shan ◽  
Rongrong Liu ◽  
Hanxiao Feng ◽  
Fei Meng ◽  
Muhanmmad Aizaz ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Critical Role ◽  
Functional Characterization ◽  
Head Kidney ◽  
Poly I:C ◽  
Future Research ◽  
Free Ribosome ◽  
Early Endosomes ◽  
Localization Analysis

AbstractToll-like receptor 19 (Tlr19) is a fish-specific TLR that plays a critical role in innate immunity. In the present study, we aimed to identify tlr19 from common carp (Cyprinus carpio L.) and explored its expression profile, localization, adaptor, and signaling pathways. A novel tlr19 cDNA sequence (Cctlr19) was identified in common carp. Phylogenetic analysis revealed that CcTlr19 was most closely related to Danio rerio Tlr19. Subcellular localization analysis indicates that CcTlr19 was synthesized in the free ribosome and then transported to early endosomes. Cctlr19 was constitutively expressed in all the examined tissues, with the highest expression in the brain. After poly(I:C) and Aeromonas hydrophila injection, the expression of Cctlr19 was significantly upregulated in immune-related organs. In addition, the expression of Cctlr19 was upregulated in head kidney leukocytes (HKL) upon stimulation with different ligands. Immunofluorescence and luciferase analyses indicate that CcTlr19 recruited TRIF as an adaptor. Furthermore, CcTlr19 can activate the expression of ifn-1 and viperin. Taken together, these findings lay the foundation for future research to investigate the mechanisms underlying fish tlr19.

scholarly journals Molecular characterization and immune functional analysis of IRF2 in common carp (Cyprinus carpio L.): different regulatory role in the IFN and NF-κB signalling pathway

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hua Li ◽  
Xinping Chen ◽  
Yaoyao Zhu ◽  
Rongrong Liu ◽  
Linlin Zheng ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Head Kidney ◽  
Ctenopharyngodon Idella ◽  
Poly I:C ◽  
Luciferase Reporter ◽  
Polyinosinic:Polycytidylic Acid ◽  
Antiviral Innate Immunity ◽  
And Control ◽  
Dual Luciferase Reporter Assay

Abstract Background Interferon regulatory factor 2 (IRF2) is an important transcription factor, which can regulate the IFN response and plays a role in antiviral innate immunity in teleost. Results In the present study, the full-length cDNA sequence of IRF2 (CcIRF2) was characterized in common carp (Cyprinus carpio L.), which encoded a protein containing a conserved DNA-binding domain (DBD) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF2 was most closely related with IRF2 of Ctenopharyngodon idella. CcIRF2 transcripts were detectable in all examined tissues, with higher expression in the gills, spleen and brain. CcIRF2 expression was upregulated in immune-related tissues of common carp upon polyinosinic:polycytidylic acid (poly (I:C)) and Aeromonas hydrophila stimulation and induced by poly (I:C), lipopolysaccharide (LPS), peptidoglycan (PGN) and flagellin in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs). In addition, overexpression of CcIRF2 decreased the expression of IFN and IFN-stimulated genes (ISGs), and a dual-luciferase reporter assay revealed that CcIRF2 could increase the activation of NF-κB. Conclusions These results indicate that CcIRF2 participates in antiviral and antibacterial immune response and negatively regulates the IFN response, which provide a new insight into the regulation of IFN system in common carp, and are helpful for the prevention and control of infectious diseases in carp farming.

scholarly journals Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohd Izwan Bin Zainol ◽  
Takumi Kawasaki ◽  
Warunthorn Monwan ◽  
Motoya Murase ◽  
Takuya Sueyoshi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Poly I:C ◽  
Type I ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Mrna Stabilization ◽  
Human Antigen R ◽  
Polycytidylic Acid ◽  
Endosomal Acidification

AbstractToll-like receptor 3 (TLR3) recognizes double-stranded RNA derived from virus and its synthetic analogue, polyinosinic–polycytidylic acid [poly(I:C)]. Upon poly(I:C) binding, TLR3 activates transcription factors to express inflammatory cytokines and type I interferon. TLR3 is located in the endosomes and its recognition of poly(I:C) and activation of downstream signaling is regulated by endosomal acidification. However, the mechanism of post-transcriptional regulation in TLR3-mediated innate responses remains unclear. Here, we focused on Human antigen R (HuR, also known as ELAVL1) that recognizes and binds to the 3′ untranslated regions (3′UTRs) of target mRNAs, thereby protecting them from mRNA degradation, and found that HuR-deficient murine macrophage cells showed significantly reduced Ifnb1 mRNA expression after poly(I:C) stimulation. HuR-deficient cells also showed a marked reduction in the expression of Atp6v0d2 mRNA, which encodes a subunit of vacuolar-type H+ ATPase (V-ATPase), and therefore reduced endosomal acidification. HuR associated with the 3′UTR of Atp6v0d2 mRNA and the stability of Atp6v0d2 mRNA was maintained by its association with HuR. Taken together, our results suggest that HuR stabilizes Atp6v0d2 mRNA, which is required for the TLR3-mediated innate immune responses.

scholarly journals SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 530
Author(s):  
Soo Jin Oh ◽  
Ok Sarah Shin
Keyword(s):  
Nucleocapsid Protein ◽  
Nuclear Translocation ◽  
Nonstructural Protein ◽  
Poly I:C ◽  
Interferon Response ◽  
Type I ◽  
Antiviral Immune Response ◽  
N Protein ◽  
Nonstructural Protein 1 ◽  
Polycytidylic Acid

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.

TLR3 activation stimulates cytokine secretion without altering agonist-induced human small airway contraction or relaxation

2009 ◽  
Vol 297 (3) ◽  
pp. L530-L537 ◽  
Author(s):  
Philip R. Cooper ◽  
Roberta Lamb ◽  
Nicole D. Day ◽  
Patrick J. Branigan ◽  
Radhika Kajekar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Lung ◽  
Small Airway ◽  
Innate Immune ◽  
Cytokine Secretion ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Healthy Human ◽  
Chronic Lung Diseases ◽  
Polycytidylic Acid

Respiratory infections exacerbate chronic lung diseases promoting airway inflammation and hyperreactivity. Toll-like receptor 3 (TLR3) recognizes viral double-stranded (ds) RNA such as polyinosinic-polycytidylic acid [poly(I:C)] and stimulates innate immune responses. The objective of this study was to test the hypothesis that dsRNA promotes lung inflammation and alters airway responsiveness to cholinergic and β-adrenergic receptor agonists in human lung slices. Human airway smooth muscle (ASM) was incubated for 24 h in poly(I:C) ± TNFα and a TLR3 monoclonal antibody. Precision-cut lung slices (PCLS; 250-μm thickness) from healthy human lungs containing a small airway were incubated in 0, 10, or 100 μg/ml poly(I:C) for 24 h. Intravital microscopy of lung slices was used to quantify contractile and relaxation responsiveness to carbachol and isoproterenol, respectively. Supernatants of ASM and PCLS were analyzed for cytokine secretion using a 25-multiplex bead assay. In human ASM, poly(I:C) (0.5 μg/ml) increased macrophage inflammatory protein-1α (MIP-1α) and RANTES that was prevented by a TLR3 monoclonal receptor antibody. Incubation of human PCLS with poly(I:C) (10 and 100 μg/ml) had little effect on the log EC50 or maximum drug effect (Emax) for contraction and relaxation in response to carbachol and isoproterenol, respectively. The responsiveness of the same human PCLS to poly(I:C) incubation was confirmed by the robust increase in chemokines and cytokines. In separate experiments, incubation of PCLS with IL-13 or TNFα (100 ng/ml) increased airway sensitivity to carbachol. Poly(I:C) promotes inflammatory mediator release that was not associated with enhanced bronchoconstriction or attenuated bronchodilation in normal healthy human lung slices. Transduction at the TLR3 initiated by dsRNA stimulates downstream innate immune responses.

scholarly journals Synergistic benefit in inflammatory arthritis by targeting IκB kinase ϵ and interferon β

2008 ◽  
Vol 68 (2) ◽  
pp. 257-263 ◽  
Author(s):  
M Corr ◽  
D L Boyle ◽  
L Ronacher ◽  
N Flores ◽  
G S Firestein
Keyword(s):  
Gene Expression ◽  
Low Dose ◽  
Serum Levels ◽  
Poly I:C ◽  
Type I ◽  
Wild Type ◽  
Polycytidylic Acid ◽  
Iκb Kinase ◽  
Novel Approach ◽  
Clinical Arthritis

Objectives:The IκB kinase (IKK)-related kinase IKKϵ regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKϵ in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis.Methods:IKKϵ–/–, IFNα∼βR–/– and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Results:Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα∼βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKϵ null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKϵ null mice. Articular chemokine gene expression was reduced in the IKKϵ–/– mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKϵ–/– mice.Conclusions:Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKϵ deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKϵ inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.

scholarly journals HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections

2017 ◽  
Vol 214 (11) ◽  
pp. 3263-3277 ◽  
Author(s):  
Lei Sun ◽  
Zhengfan Jiang ◽  
Victoria A. Acosta-Rodriguez ◽  
Michael Berger ◽  
Xin Du ◽  
...  
Keyword(s):  
Viral Infections ◽  
Poly I:C ◽  
Type I ◽  
Induced Mutations ◽  
Herpes Simplex Virus 1 ◽  
Double Stranded Rna ◽  
Polycytidylic Acid ◽  
Interferon Regulatory Factor 1 ◽  
Mouse Macrophages ◽  
Simplex Virus

Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea–induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.

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