Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2007
Publication Date: 4/19/2007
Citation: Chiou, P.P., Lin, C., Bols, N.C., Chen, T.T. 2007. Characterization of virus/double-stranded RNA-dependent induction of antimicrobial peptide hepcidin in trout macrophages. Developmental and Comparative Immunology. 31:1297-1309. Interpretive Summary: Each year, aquaculture losses due to disease outbreaks as the consequence of bacterial or viral infection is extremely significant. There is an urgent need to develop innovative technology to resolve this problem. Although naturally occurring antimicrobial peptides are known to control the propagation of pathogenic microorganisms, the relationship of these peptides to the immune system of the host is not fully understood. In mammals, hepcidin, an antimicrobial peptide, is induced by bacterial infection. We addressed the question whether hepcidin could be induced in rainbow trout. This was done using macrophage cells treated with polyinosinic-polycytidylic acid, a mimic of viral double-stranded RNA, or injecting trout with the same compound. Our results showed that high levels of hepcidine were readily produced in trout macrophage cells and whole fish treated with polyinosinic-polycytidylic acid. This is the first time that hepcidin, one of the known antimicrobial peptides, can be induced by infection with an RNA fish virus. Further studies in this system will shed light on how to manipulate naturally occurring antimicrobial peptides to control infection in fish by viral pathogens.
Technical Abstract: Hepcidin is an antimicrobial peptide responsive to bacterial infection. We report the characterization of a virus/doublestranded 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 ematopoietic 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.