Zebrafish models of innate immunity

Diseases of immunity cause much illness in the developed world – on one hand we are beset by a range of antibiotic resistance bacterial infections, while on the other hand our immune systems are responsible for many the common diseases of ageing – heart disease, stroke and COPD. Understanding the regulation of innate immune cells, neutrophils and macrophages, in infection and inflammation will help us tune the immune system to the exact level needed to cope with the current level of threat. More host defence to fight antibiotic resistant organisms; less host defence to prevent lung damage in response to environmental pollutants. To improve our understanding, I have set up a model system in which the genes controlling regulation of innate immune cell function can be identified. The model I have chosen is the Zebrafish, which is both genetically manipulable and transparent, leading to easy visualisation of immune cells during infection and inflammation. This model allows me to test the ability of a range of candidate genes to influence host-pathogen interaction and the resolution of inflammation, and additionally to screen for novel genes involved in this process. At the same time, I can see every immune cell during the whole of an infection or an inflammatory episode, where necessary imaging intracellular signalling events in real-time. The small size of our model also lends itself to drug screening and this has identified several potential new therapies for immune disease. I will discuss how this model has informed our understanding of inflammation, sharing new data on regulation of neutrophil function in vivo.