Molecular characterization of nucleotide binding and oligomerization domain (NOD)-2, analysis of its inductive expression and down-stream signaling following ligands exposure and bacterial infection in rohu (Labeo rohita)

Dev Comp Immunol. 2012 Jan;36(1):93-103. doi: 10.1016/j.dci.2011.06.018. Epub 2011 Jul 13.

Abstract

Nucleotide-binding and oligomerization domain (NOD)-2 is a cytoplasmic pattern recognition receptor (PRR) and is a member of NOD like receptor (NLR) family. It senses a wide range of bacteria and viruses or their products and is involved in innate immune responses. In this report, NOD-2 gene was cloned and characterized from rohu (Labeo rohita) which is highly commercially important fish species in the Indian subcontinent. The full length rohu NOD-2 (rNOD-2) cDNA comprised of 3176 bp with a single open reading frame (ORF) of 2949 bp encoding a polypeptide of 982 amino acids (aa) with an estimated molecular mass of 109.65 kDa. The rNOD-2 comprised two N-terminal CARD domains (at 4-91 aa and 111-200 aa), one NACHT domain (at 271-441 aa) and seven C-terminal leucine rich repeat (LRR) regions. Phylogenetically, rNOD-2 was closely related to grass carp NOD-2 (gcNOD2) and exhibited significant similarity (94.2%) and identity (88.6%) in their amino acids. Ontogeny analysis of rNOD-2 showed its constitutive expression across the developmental stages, and highlighted the embryonic innate defense system in fish. Tissue specific analysis of rNOD-2 by quantitative real-time PCR (qRT-PCR) revealed its wide distribution; highest expression was in liver followed by blood. In response to PGN and LTA stimulation, Aeromonas hydrophila and Edwardsiella tarda infection, and poly I:C treatment, expression of rNOD-2 and its associated downstream molecules RICK and IFN-γ were significantly enhanced in the treated fish compared to control. These findings suggested the key role of NOD-2 in augmenting innate immunity in fish in response to bacterial and viral infection. This study may be helpful for the development of preventive measures against infectious diseases in fish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aeromonas hydrophila / immunology*
  • Aeromonas hydrophila / pathogenicity
  • Amino Acid Sequence
  • Animals
  • Carps*
  • Cells, Cultured
  • Cloning, Molecular
  • Edwardsiella tarda / immunology*
  • Edwardsiella tarda / pathogenicity
  • Evolution, Molecular
  • Fish Proteins / genetics*
  • Fish Proteins / immunology
  • Fish Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology
  • Gram-Negative Bacterial Infections / immunology*
  • Immunity, Innate
  • Ligands
  • Molecular Sequence Data
  • Nod2 Signaling Adaptor Protein / genetics*
  • Nod2 Signaling Adaptor Protein / immunology
  • Nod2 Signaling Adaptor Protein / metabolism
  • Phylogeny
  • Signal Transduction / immunology

Substances

  • Fish Proteins
  • Ligands
  • Nod2 Signaling Adaptor Protein