Bacteria-induced IL-1β and its receptors in snakehead (Channa argus): Evidence for their involvement in antibacterial innate immunity

As a central pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1 beta has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1 beta. In this study, snakehead (Channa argus) IL-1 beta (shIL-1 beta) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized. ShIL-1 beta contained the IL-1 family signature domain, and a potential cutting site at Asp 96 that presented in all vertebrate IL-1 beta sequences. ShIL-1R1 had three extracellular IG-like domains and one intracellular signal TIR domain, while shIL-1R2 had three extracellular IG-like domain but lacked the intracellular signal TIR domain. ShIL-1 beta, shIL-1R1, and shIL-1R2 were constitutively expressed in all tested tissues, and their expressions could be induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo, and by LTA, LPS, and Poly (I:C) in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shIL-1 beta upregulated the expression of endogenous shIL-1 beta, shIL-R1, and shIL-R2 in snakehead HKLs, and enhanced intracellular bactericidal activity. Taken together, this study found that, like IL-1 beta and its receptors in mammals, shIL-1 beta and its receptors play crucial roles in antibacterial innate immunity. This provides new insight into the evolution of IL-1 beta function in vertebrates.