The role of gamma interferon in innate immunity in the zebrafish embryo

Abstract

SUMMARY The zebrafish genome contains ten genes that encode class II cytokine-like peptides, of which the two that are related most closely to mammalian interferon gamma (IFN-γ) were named IFN-γ1 and IFN-γ2. Although the zebrafish has become a popular model system to study immune mechanisms, and although interferons are central regulators of immunity, which zebrafish cytokines correspond functionally to mammalian IFN-γ has not been established. We used zebrafish embryos to assay the functions of IFN-γ1 and IFN-γ2, and have identified a subset of zebrafish homologs of the mammalian IFN-responsive genes as IFN-γ targets in the zebrafish embryo: these genes are upregulated in response to raised levels of either IFN-γ1 or IFN-γ2. Infection studies using two different pathogens show that IFN-γ signalling is required for resistance against bacterial infections in the young embryo and that the levels of IFN-γ need to be regulated tightly: raising IFN-γ levels sensitizes fish embryos against bacterial infection. Embryos injected with high doses of Escherichia coli are able to clear the bacteria within a day, and the γ-interferons are necessary for this defence reaction. The protective response to Yersinia ruckeri, a natural fish pathogen that is lethal at low doses, also requires IFN-γ. As in the induction of target genes, the two interferons act at least partly redundantly. Together with the previously demonstrated type III interferon response, these results show that the counterparts of the mammalian viral and bacterial interferon-dependent defence functions are in place in zebrafish embryos, and suggest that zebrafish IFN-γ1 and IFN-γ2 are functionally equivalent to mammalian IFN-γ.

In Vivo Analysis of Ifn-γ1 and Ifn-γ2 Signaling in Zebrafish

“…Recent in vivo studies on Ifn-g target gene induction showed that the response elicited by Ifn-g1 and Ifn-g2, as measured by target gene induction, was identical for both Ifn-g (14). Morpholino-mediated knockdown of either one of the ifn-g genes does not render the embryos susceptible to bacterial infection.…”

Expression analysis of three immune genes Interferon-gamma, Mx and Interferon regulatory factor-1 of Japanese flounder ( Paralichthys olivaceus )

“…IFNs are best known for their vital roles in innate immune system. Recently, studies focused on the immune-related functions of IFN-γ had been carried out in many teleosts, such as goldfish 42 and zebrafish 10 . We have carried out the expression analysis of the Japanese flounder IFN-γ in tissues infected with LPS and revealed the expression regularity.…”

“…Interferon (IFN) which plays an important role in innate immune system is a protein secreted from cells in response to invasion by pathogens and virus. In mammals, IFN is classified into type-I IFN (α, β, ε, δ, τ and ω), type-II IFN (γ) and type-III IFN (λ) based on their differences in primary structure, serology and their most likely time of evolutionary divergence 8,9,10 . Interferon-gamma (IFN-γ) is a pleiotropic proinflammatory and antiviral cytokine, which was initially identified in PHA-activated mammalian lymphocyte supernatants 11 .…”

Fish viperin exerts a conserved antiviral function through RLR-triggered IFN signaling pathway

“…In zebrafish, there are four members of type I IFNs (Aggad et al, 2009;Lopez-Munoz et al, 2009), and two members of type II IFNs, IFNc1 and IFNc2 (Igawa et al, 2006;Sieger et al, 2009). Previously we confirmed both types of zebrafish IFNs activate zebrafish IRF9 promoter in epithelioma papulosum cyprini cells (EPC) (Shi et al, 2013).…”

“…For example, zebrafish Danio rerio genome has four IFNu genes (DrIFNu1/ 2/3/4, or named DrIFN1/2/3/4) most similar to mammalian type I IFN, and two IFNc genes (DrIFNc1/2) orthologous to mammalian type II IFN (Aggad et al, 2009;Lopez-Munoz et al, 2009;Sieger et al, 2009). To determine whether two types of fish IFNs could induce crucian carp viperin expression, the roles of these zebrafish IFNs in activation of crucian carp viperin promoter and induction of viperin mRNA and proteins were investigated.…”