NOD2 in zebrafish functions in antibacterial and also antiviral responses via NF-κB, and also MDA5, RIG-I and MAVS

Zou, P.F., Chang, M.X., Li, Y., Xue, N.N., Li, J.H., Chen, S.N., Nie, P.
Fish & shellfish immunology   55: 173-85 (Journal)
Registered Authors
Chang, Mingxian, Nie, Pin
NF-kappaB, NOD2, Nod-like receptor, RLR, Zebrafish
MeSH Terms
  • Animals
  • Anti-Bacterial Agents/metabolism*
  • Antiviral Agents/metabolism*
  • Edwardsiella tarda/physiology
  • Enterobacteriaceae Infections/genetics
  • Enterobacteriaceae Infections/microbiology
  • Enterobacteriaceae Infections/veterinary
  • Fish Diseases/genetics*
  • Fish Diseases/microbiology
  • Fish Diseases/virology
  • Nod2 Signaling Adaptor Protein/genetics*
  • Nod2 Signaling Adaptor Protein/metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases/genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
  • Rhabdoviridae/physiology
  • Rhabdoviridae Infections/genetics
  • Rhabdoviridae Infections/veterinary
  • Rhabdoviridae Infections/virology
  • Zebrafish*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
27235368 Full text @ Fish Shellfish Immunol.
NOD2/RIPK2 signalling plays essential role in the modulation of innate and adaptive immunity in mammals. In this study, NOD2 was functionally characterized in zebrafish (Danio rerio), and its interaction with a receptor-interaction protein, RIPK2, and RLRs such as MDA5 and RIG-I, as well as the adaptor, MAVS was revealed in fish innate immunity. The expression of NOD2 and RIPK2 in ZF4 cells has been constitutive and can be induced by the infection of Edwardsiella tarda and SVCV. The NOD2 can sense MDP in PGN from Gram-negative and -positive bacteria. It is further revealed that the NOD2 and RIPK2 can activate NF-κB and IFN promoters, inducing significantly antiviral defense against SVCV infection. As observed in the reduced bacterial burden in RIPK2 overexpressed cells, RIPK2 also has a role in inhibiting the bacterial replication. The overexpression of NOD2 in zebrafish embryos resulted in the increase of immune gene expression, especially those encoding PRRs and cytokines involved in antiviral response such as MDA5, RIG-I, and type I IFNs, etc. Luciferase reporter assays and co-immunoprecipitation assays demonstrated that zebrafish NOD2 is associated with MDA5 and RIG-I in signalling pathway. In addition, it is further demonstrated that RIPK2 and MAVS in combination with NOD2 have an enhanced role in NOD2-mediated NF-κB and type I IFN activation. It is concluded that teleost fish NOD2 can not only sense MDP for activating innate immunity as reported in mammals, but can also interact with other PRRs to form a network in antiviral innate response.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes