Why study infection & inflammation in the zebrafish?
Figure 1: zebrafish with red fluorescent macrophages and green fluorescent neutrophils (image Meijer lab)
All vertebrates, from fish to mammals, have a very similar immune system. Zebrafish are transparent during their early life stages, which makes them optimally suited for non-invasive imaging of the behavior of immune cells during development and disease (Figure 1). Zebrafish are also extremely useful for large-scale genetic and chemical screens. Due to these unique features the zebrafish model has become widely used by investigators who are interested in the basic molecular mechanisms that regulate the function of immune cells and by those who study diseases caused by infection or by defects in the immune system, such as chronic inflammatory disorders and autoimmune disease.
In recent years, zebrafish models have been developed for a wide variety of bacterial, viral, fungal, and protozoan infections. Many of these models mimic key aspects of human infectious disease. A good example is the zebrafish model for tuberculosis, which has led to important new insights that have inspired new strategies for the treatment of patients (Figure 2).
Figure 2: Mycobacterium infection in zebrafish recapitulates key features of human tuberculosis. This includes the intracellular survival of the bacteria in macrophages and the formation of granulomas: localized areas of inflammation in the tissue. Transparent zebrafish embryos and larvae are very useful to study the early stages of granuloma formation by the major cell types of the innate immune system: macrophages (blue) and neutrophils (green). Granulomas in adult fish also attract lymphocytes (red), which are essential to contain the infection. (figure Meijer lab).
Inflammation is an essential response of the immune system that functions in wound repair and in defense against invading microbes. However, inflammation must be tightly controlled since excessive inflammation can cause extensive tissue damage and exacerbate infections. Inflammatory and autoimmune defects are the underlying cause of many diseases such as asthma, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and diabetes. Recent advances in our understanding of the initiation and resolution of inflammation have been made by investigators combining genetic technologies with in vivo imaging of immune cell lineages in zebrafish (Figure 3).
Figure 3: The zebrafish immune system. Development of myeloid and lymphoid cell lineages is highly conserved between fish and mammals. Fluorescent reporter lines for the different cell types facilitate live imaging in zebrafish models. (figure Huttenlocher lab). Recent reporter lines for macrophages take advantage of the mpeg1 promoter.