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Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signal...

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Autores principales: Nie, Li, Xu, Xiao-Xiao, Xiang, Li-Xin, Shao, Jian-Zhong, Chen, Jiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485971/
https://www.ncbi.nlm.nih.gov/pubmed/28555019
http://dx.doi.org/10.3390/ijms18061147
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author Nie, Li
Xu, Xiao-Xiao
Xiang, Li-Xin
Shao, Jian-Zhong
Chen, Jiong
author_facet Nie, Li
Xu, Xiao-Xiao
Xiang, Li-Xin
Shao, Jian-Zhong
Chen, Jiong
author_sort Nie, Li
collection PubMed
description Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signaling pathways. However, the relationship between these PRRs, especially in teleost fish models, is rarely reported. In this article, we describe the mutual regulation of zebrafish NOD2 (DrNOD2) and RIG-I (DrRIG-I) in innate immune responses. Luciferase assays were conducted to determine the activation of NF-κB and interferon signaling. Morpholino-mediated knockdown and mRNA-mediated rescue were performed to further confirm the regulatory roles between DrNOD2 and DrRIG-I. Results showed that DrNOD2 and DrRIG-I shared conserved structural hallmarks with their mammalian counterparts, and activated DrRIG-I signaling can induce DrNOD2 production. Surprisingly, DrNOD2-initiated signaling can also induce DrRIG-I expression, indicating that a mutual regulatory mechanism may exist between them. Studies conducted using HEK293T cells and zebrafish embryos showed that DrRIG-I could negatively regulate DrNOD2-activated NF-κB signaling, and DrNOD2 could inhibit DrRIG-I-induced IFN signaling. Moreover, knocking down DrRIG-I expression by morpholino could enhance DrNOD2-initiated NF-κB activation, and vice versa, which could be rescued by their corresponding mRNAs. Results revealed a mutual feedback regulatory mechanism underlying NOD2 and RIG-I signaling pathways in teleosts. This mechanism reflects the coordination between cytosolic antibacterial and antiviral PRRs in the complex network of innate immunity.
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spelling pubmed-54859712017-06-29 Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways Nie, Li Xu, Xiao-Xiao Xiang, Li-Xin Shao, Jian-Zhong Chen, Jiong Int J Mol Sci Communication Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signaling pathways. However, the relationship between these PRRs, especially in teleost fish models, is rarely reported. In this article, we describe the mutual regulation of zebrafish NOD2 (DrNOD2) and RIG-I (DrRIG-I) in innate immune responses. Luciferase assays were conducted to determine the activation of NF-κB and interferon signaling. Morpholino-mediated knockdown and mRNA-mediated rescue were performed to further confirm the regulatory roles between DrNOD2 and DrRIG-I. Results showed that DrNOD2 and DrRIG-I shared conserved structural hallmarks with their mammalian counterparts, and activated DrRIG-I signaling can induce DrNOD2 production. Surprisingly, DrNOD2-initiated signaling can also induce DrRIG-I expression, indicating that a mutual regulatory mechanism may exist between them. Studies conducted using HEK293T cells and zebrafish embryos showed that DrRIG-I could negatively regulate DrNOD2-activated NF-κB signaling, and DrNOD2 could inhibit DrRIG-I-induced IFN signaling. Moreover, knocking down DrRIG-I expression by morpholino could enhance DrNOD2-initiated NF-κB activation, and vice versa, which could be rescued by their corresponding mRNAs. Results revealed a mutual feedback regulatory mechanism underlying NOD2 and RIG-I signaling pathways in teleosts. This mechanism reflects the coordination between cytosolic antibacterial and antiviral PRRs in the complex network of innate immunity. MDPI 2017-05-27 /pmc/articles/PMC5485971/ /pubmed/28555019 http://dx.doi.org/10.3390/ijms18061147 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Nie, Li
Xu, Xiao-Xiao
Xiang, Li-Xin
Shao, Jian-Zhong
Chen, Jiong
Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title_full Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title_fullStr Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title_full_unstemmed Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title_short Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways
title_sort mutual regulation of nod2 and rig-i in zebrafish provides insights into the coordination between innate antibacterial and antiviral signaling pathways
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485971/
https://www.ncbi.nlm.nih.gov/pubmed/28555019
http://dx.doi.org/10.3390/ijms18061147
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