Multiple Hepcidins in a Teleost Fish, Dicentrarchus labrax: Different Hepcidins for Different Roles

Abstract

Teleost fish rely heavily on their innate immunity for an adequate response against pathogens and environmental challenges, with the production of antimicrobial peptides being one of their first lines of defense. Among those is hepcidin, a small cysteine-rich antimicrobial peptide that is also the key regulator of iron metabolism. Although most mammals possess a single hepcidin gene, with a dual role in both iron metabolism regulation and antimicrobial response, many teleost fish present multiple copies of hepcidin, most likely because of genome duplications and positive Darwinian selection, suggesting that different hepcidins may perform different functions. To study the roles of hepcidin in teleost fish, we have isolated and characterized several genes in the European sea bass (Dicentrarchus labrax) and evaluated variations in their expression levels in response to different experimental conditions. Although several hepcidin genes were found, after phylogenetic analysis they could be clustered in two groups: hamp1-like, with a single isoform similar to mammalian hepcidins, and hamp2-like, with several isoforms. Under experimental conditions, hamp1 was upregulated in response to iron overload and infection and downregulated during anemia and hypoxic conditions. Hamp2 did not respond to either iron overload or anemia but was highly upregulated during infection and hypoxia. In addition, Hamp2 synthetic peptides exhibited a clear antimicrobial activity against several bacterial strains in vitro. In conclusion, teleost fish that present two hepcidin types show a degree of subfunctionalization of its functions, with hamp1 more involved in the regulation of iron metabolism and hamp2 mostly performing an antimicrobial role.

CXCR3.1 and CXCR3.2 Differentially Contribute to Macrophage Polarization in Teleost Fish

“…In teleost fish, innate immunity is also the first line of defense against pathogens (68). Although the adaptive immunity of teleosts is weak, they possess more diverse innate immune molecules than do mammals (34,69). Macrophage dysfunction is related to the survival of septic mice and teleost fish (38,43).…”

“…In vertebrate evolution, gene duplications produce redundant genes, which are associated with adaptive radiations in teleosts (32,33). These redundant genes may result in subfunctionalization, as in the case of sea bass (Dicentrarchus labrax), in which different hepcidins exhibit different roles (34). In this study, we found that CXCR3.1 and CXCR3.2 were expressed in the macrophages of the teleosts: ayu (Plecoglossus altivelis), grass carp (Ctenopharyngodon idella), and spotted green pufferfish (Tetraodon nigroviridis).…”

Ontogeny and modulation after PAMPs stimulation of β-defensin, hepcidin, and piscidin antimicrobial peptides in meagre ( Argyrosomus regius )

“…Studies in fish species of Hep protein have shown multiple isoforms exist and these are classified into two groups: Hamp type and Hamp type 2. One Hep isoform has iron regulatory roles sharing a high degree of homology with mammalian counterparts, and the second Hep copy has retained only the antimicrobial role [9,49]. Phylogenetic analysis in this study has shown the isoform identified in meagre is more similar to Hamp 2 and likely does not retain the iron regulatory functions.…”

Molecular characterization and expression analysis of hepc1 and hepc2 in three tilapia species collected from Lake Manzala

“…Fish have developed several defense mechanisms against waterborne pathogens with one of the first lines of defense consisting relatively small peptides called antimicrobial peptides (AMPs) (Neves et al 2015). Antimicrobial peptides are identified as a positively charged molecules with short amino acid chains which play crucial roles in host defense against pathogens through antimicrobial actions or immunomodulatory functions (Jenssen et al 2006).…”