Innate Immune System of the Zebrafish Danio rerio

Con Sullivan and Carol H. Kim(*)

1 Overview 114

2 Components of Innate Immunity 115

2.1 General Description 115

2.2 Drosophila Toll: Identification and Recognition of a Dually

Functioning Pathway 116

2.3 TLRs and TIR-Bearing Adaptor Proteins 117

3 Zebrafish as a Model for Infectious Disease and Innate Immune Responses 118

3.1 Overview 118

3.2 Forward and Reverse Genetics 119

3.3 An Infectious Disease and Innate Immunity Model 120

4 NK-Like Cells 122

5 Additional Innate Immunity Receptors in Zebrafish 124

6 Zebrafish Phagocytes 126

7 Conclusion 126

References 127

Abstract There has been a revolution in immunology in recent years that has transformed the paradigmatic underpinnings of vertebrate immunology to include the innate immune response. The utilization of basally diverging model systems, like the zebrafish, provides particular insight into the origins and evolution of vertebrate immunity. Investigations aimed at exposing the breadth and complexity of innate immunity using the zebrafish model system have uncovered a broad spectrum of mechanisms, both novel and conserved, that add depth to our understanding of how the immune system functions. Of particular significance is the fact that, during the first 4-6 weeks of development, the zebrafish relies upon innate immunity as its sole mechanism of defense. This unique characteristic, combined with the zebrafish model's inherent advantages including high fecundity, external development, and optical transparency during early development, make the zebrafish a particularly attractive model of study. The establishment

Department of Biochemistry, Microbiology, and Molecular Biology, University of Maine, Orono, ME 04469, USA, [email protected]

H. Heine (ed.), Innate Immunity of Plants, Animals, and Humans. Nucleic Acids and Molecular Biology 21. © Springer-Verlag Berlin Heidelberg 2008

of bacterial and viral infectious disease models such as Edwardsiella tarda and snakehead rhabdovirus, respectively, as well as the addition of a wide range of reagents and techniques, including robust forward and reverse genetics approaches, have facilitated the zebrafish model's usage to study of a variety of innate immunity questions. Close examination of the zebrafish's innate immune system reveals a strong degree of sequence conservation in many of areas of study, including but not limited to pattern recognition receptors like the Toll-like receptors, their pathway components, and a variety of cytokines. Studies are currently underway to determine whether such sequence homology equates to functional homology. In addition, a variety of zebrafish genes encoding proteins of unique function are currently under study, including assorted lectins and novel immune type receptors. Close examination of these genes may provide needed insight into the evolutionary history of immunity in vertebrates. In its totality, the zebrafish is a vibrant and useful model system with the potential to offer immunologists alternative perspectives into the underlying mechanisms of vertebrate innate immunity, particularly during its early life, when innate immune responses are all that can be mustered.

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