Novel insights into the immune regulatory effects of ferritins from blunt snout bream, Megalobrama amblycephala

Abstract

Ferritins play vital roles in maintenance of iron homeostasis as iron storage proteins. Recently, the immune function of ferritins have attracted increasing attention, especially their roles in defense against pathogenic infections. However, the immune regulatory mechanism of fish ferritins are not well known. In the present study, comparative digital gene expression (DGE) profiling was performed to explore the regulatory effects of the Megalobrama amblycephala ferritins (MamFers) using MamFers overexpressed and control L8824 cells (Ctenopharyngodon idella hepatic cell line). Clean reads were aligned to the C. idella genome and differential expression analysis was conducted with representative differentially expressed genes pointed out. On that basis, further studies were performed to verify two pivotal regulated pathways in L8824 and EPC (Epithelioma Papulosum Cyprini cell line) cells, respectively. The results showed that NLRC5 (NOD-like Receptor Family CARD Domain Containing 5) mediated the regulation of MamFers on expression of MHC I (Major Histocompatibility Complex Class I) and its chaperone β2M (Beta-2-Microglobulin) in L8824 cells. Then, β2M further mediated the regulation of MamFers on hepcidin expression, indicating that MamFers regulated the expression of hepcidin via NLRC5/MHC I/β2M axis. In addition, MamFers regulated the adhesion of Aeromonas hydrophila to EPC cells by regulating the expression of two extracellular matrix proteins Intgβ1 (integrin β1) and FN (fibronectin). In a word, the present study provided novel insights into the immune regulatory functions of fish ferritins.