Infectious disease models in zebrafish

In recent years, the zebrafish (Danio rerio) has developed as an important alternative to mammalian models for the study of hostpathogen interactions. Because they lack a functional adaptive immune response during the first 4e6 weeks of development, zebrafish rely upon innate immune responses to protect against injuries and infections. During this early period of development, it is possible to isolate and study mechanisms of infection and inflammation arising from the innate immune response without the complications presented by the adaptive immune response. Zebrafish possess several inherent characteristics that make them an attractive option to study hostpathogen interactions, including extensive sequence and functional conservation with the human genome, optical clarity in larvae that facilitates the high-resolution visualization of host cellemicrobe interactions, a fully sequenced and annotated genome, robust forward and reverse genetic tools and techniques (e.g., CRISPR-Cas9 and TALENs), and amenability to chemical studies and screens. Here, we describe methods for studying hostpathogen interactions both through systemic infections and through localized infections that allow analysis of host cell response, migration patterns, and behavior. Each of the methods described can be modified for use in downstream applications that include ecotoxicant studies and chemical screens.