Stimulation of type I IFN activity in Atlantic salmon (Salmo salar L.) leukocytes: synergistic effects of cationic proteins and CpG ODN.

Unmethylated CpG motifs in DNA are recognised by vertebrate immune cells as pathogen signatures. Consequently, oligodeoxynucleotides containing CpG motifs (CpG ODNs) are able to enhance and direct immune responses. Recent studies have demonstrated that CpG ODNs activate antiviral immune responses in Atlantic salmon (Salmo salar L.) leukocytes, and are therefore promising agents as vaccine adjuvants or immunostimulants in fish. In this work, we report synergy of CpG ODN and cationic proteins in the stimulation of type I IFN activity in Atlantic salmon leukocytes. Different fractions of cationic histone proteins derived from cod milt or poly-l-arginine and poly-l-lysine were screened for their ability to enhance CpG ODN induced type I IFN activity in Atlantic salmon leukocytes. Optimal ratio of histones to CpG ODN was identified, and effects on transcription of type I IFN and antiviral Mx genes were studied. Delivery of CpG ODN with cationic proteins enhanced the production of type I IFN and succeeding Mx transcripts after two and five days of stimulation at substimulatory concentrations of CpG ODN. These results indicate that co-delivery of CpG ODN and cationic proteins enhance antiviral mechanisms in Atlantic salmon leukocytes as compared to CpG ODN alone.