Innate immunity is an organism’s first line of defence against infectious pathogens. Bacterial infection induces the production of cytokines, such as interferon gamma (IFN-γ), which activate non-specific immune-mediating cells, such as macrophages and neutrophils. This type of immune response is primarily responsible for the clearance of bacteria after acute infection. However, the mammalian immune system and inflammatory response are very complex, so a simplified model for bacterial infection may allow more direct investigation of the innate immune response.
The zebrafish is quickly becoming a preferred model for many human diseases, as it is easy to manipulate and alter genetically. The zebrafish embryo does not have an adaptive immune system, which suggests that it may serve as a simple system to study pathogen-induced innate immune mechanisms. However, limited knowledge about zebrafish immune function prevents full realisation of its potential utility as a model for the mammalian immune system.
This work identifies an important signalling system involved in pathogen resistance in the zebrafish embryo, which is mediated by IFN-γ. The authors show that two interferons, IFN-γ1 and IFN-γ2, exhibit similar functions in zebrafish as in mammals, in spite of their sequence divergence. Both IFN-γ types are active in the early zebrafish embryo and are necessary for resistance to pathogens. This work establishes infection of the zebrafish by the Gram-negative bacterium Yersinia ruckeri as a tractable experimental tool to define the innate immune response to bacterial infection.
Implications and future directions
Since the function of IFN-γ signalling is conserved in the zebrafish embryo, where it is necessary for survival of the organism following bacterial infection, it should be a useful model to understand the innate immune response to infection. The zebrafish model is easily handled, maintained, observed and manipulated, both experimentally and genetically. Thus, the zebrafish embryo has potential to further define IFN-γ signalling in genetic studies of relevant immunological pathways and for screening drugs that modify these pathways.