Characterization of virus/double-stranded RNA-dependent induction of antimicrobial peptide hepcidin in trout macrophages.

Hepcidin is an antimicrobial peptide responsive to bacterial infection. We report the characterization of a virus/double-stranded RNA (dsRNA) induction of hepcidin in rainbow trout (Oncorhynchus mykiss). Increased level of hepcidin mRNA was observed in trout macrophage RTS11 cells treated with polyinosinic-polycytidylic acid (poly I:C), a mimic of viral dsRNA. The induction was also observed in poly I:C-injected trout, demonstrating that it is a bona fide biological response. The induction was not observed in livers or hepatic RTH1B2C cells despite the presence of IFN response. The induction required de novo protein synthesis. Studies on the kinetic relationship among the poly I:C-regulated hepcidin induction and IFN response indicated that the two responses were uncoupled. Interestingly, in RTS11 infected with infectious hematopoietic necrosis virus, the level of hepcidin was increased as expected but subsequently reduced to below baseline as the infection progressed, whereas IFNs, Mx1 and TLR3 were still increasing.