Zebrafish as a model for infectious disease and immune function.

The zebrafish, Danio rerio, has come to the forefront of biomedical research as a powerful model for the study of development, neurobiology, and genetics of humans. In recent years, use of the zebrafish system has extended into studies in behaviour, immunology and toxicology, retaining the concept that it will serve as a model for human disease. As one of the most thoroughly studied teleosts, with a wealth of genetic and genomic information available, the zebrafish is now being considered as a model for pathogen studies in finfishes. Its genome is currently being sequenced and annotated, and gene microarrays and insertional mutants are commercially available. The use of gene-specific knockdown of translation through morpholino oligonucleotides is widespread. As a result, several laboratories have developed bacterial and viral disease models with the zebrafish to study immune responses to infection. Although many of the zebrafish pathogen models were developed to address human infectious disease, the results of these studies should provide important clues for the development of effective vaccines and prophylactic measures against bacterial and viral pathogens in economically important fishes. In this review, the capabilities and potential of the zebrafish model system will be discussed and an overview of information on zebrafish infectious disease models will be presented.

[1]  M. Neely,et al.  Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence , 2005, Infection and Immunity.

[2]  Tohru Suzuki,et al.  Identification, cDNA cloning, and mRNA localization of a zebrafish ortholog of leukemia inhibitory factor. , 2007, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[3]  Nancy Hopkins,et al.  Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development , 2002, Nature Genetics.

[4]  J. Roach,et al.  Endotoxin recognition: In fish or not in fish? , 2005, FEBS letters.

[5]  V. Watral,et al.  Pathogenesis of Mycobacterium spp. in zebrafish (Danio rerio) from research facilities. , 2007, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[6]  P. Ingham,et al.  A transgenic zebrafish model of neutrophilic inflammation. , 2006, Blood.

[7]  K. Praveen,et al.  Constitutive expression of tumor necrosis factor-alpha in cytotoxic cells of teleosts and its role in regulation of cell-mediated cytotoxicity. , 2006, Molecular immunology.

[8]  The interferon response is involved in nervous necrosis virus acute and persistent infection in zebrafish infection model. , 2008, Molecular immunology.

[9]  Carol Kim,et al.  Molecular and Functional Analysis of an Interferon Gene from the Zebrafish, Danio rerio , 2003, Journal of Virology.

[10]  H. Heine Innate immunity of plants, animals, and humans , 2008 .

[11]  E. Kopp IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts , 2004 .

[12]  T. Akazawa,et al.  TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction , 2003, Nature Immunology.

[13]  B. Thisse,et al.  Ontogeny and behaviour of early macrophages in the zebrafish embryo. , 1999, Development.

[14]  A. Menudier,et al.  Comparative virulence between different strains of Listeria in zebrafish (Brachydanio rerio) and mice. , 1996, Pathologie-biologie.

[15]  Carol Kim,et al.  Functional characterization of full-length TLR3, IRAK-4, and TRAF6 in zebrafish (Danio rerio). , 2005, Molecular immunology.

[16]  Hannah E. Volkman,et al.  Mycobacterium marinum Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity , 2007, Infection and Immunity.

[17]  E. Brown,et al.  A Mycobacterial Operon Essential for Virulence In Vivo and Invasion and Intracellular Persistence in Macrophages , 2006, Infection and Immunity.

[18]  Zhanjiang Liu,et al.  CC chemokines in zebrafish: evidence for extensive intrachromosomal gene duplications. , 2006, Genomics.

[19]  A. Amsterdam Insertional mutagenesis in zebrafish , 2003, Developmental dynamics : an official publication of the American Association of Anatomists.

[20]  P. Witten,et al.  Characterization of Snakehead Rhabdovirus Infection in Zebrafish (Danio rerio) , 2005, Journal of Virology.

[21]  M. Caparon,et al.  Patterns of virulence gene expression differ between biofilm and tissue communities of Streptococcus pyogenes , 2005, Molecular microbiology.

[22]  T. Mak,et al.  Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Carol Kim,et al.  Effects of low concentrations of arsenic on the innate immune system of the zebrafish (Danio rerio). , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  M. Kent,et al.  Mycobacterium haemophilum infections of zebrafish (Danio rerio) in research facilities. , 2007, FEMS microbiology letters.

[25]  A. Schier,et al.  A genetic screen for mutations affecting embryogenesis in zebrafish. , 1996, Development.

[26]  C. Kimmel,et al.  Inhibition of zebrafish fgf8 pre‐mRNA splicing with morpholino oligos: A quantifiable method for gene knockdown , 2001, Genesis.

[27]  F. Martinon,et al.  RIP1 is an essential mediator of Toll-like receptor 3–induced NF-κB activation , 2004, Nature Immunology.

[28]  Carol Kim,et al.  Innate Immune System of the Zebrafish, Danio rerio , 2008 .

[29]  R. Savan,et al.  An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals. , 2006, Molecular immunology.

[30]  D A Kane,et al.  The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. , 1996, Development.

[31]  David A. Williams,et al.  Mouse model of X–linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production , 1995, Nature Genetics.

[32]  Kay Hofmann,et al.  RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. , 2004, Nature immunology.

[33]  C. Nüsslein-Volhard,et al.  Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate , 1994, Current Biology.

[34]  Zhonghe Zhou,et al.  The smallest known non-avian theropod dinosaur , 2000, Nature.

[35]  A. Xu,et al.  Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus aureus infection: striking similarities and obvious differences with mammals. , 2007, Molecular immunology.

[36]  Shizuo Akira,et al.  Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-β (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-κB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling 1 , 2003, The Journal of Immunology.

[37]  Carol Kim,et al.  Effects of Arsenic on Zebrafish Innate Immune System , 2005, Marine Biotechnology.

[38]  J. Postlethwait,et al.  Erratum: A zebrafish sox9 gene required for cartilage morphogenesis (Development vol. 129 (5065-5079)) , 2002 .

[39]  L. Steiner,et al.  Characterization and expression of the recombination activating genes (rag1 and rag2) of zebrafish , 1997, Immunogenetics.

[40]  Z. Gong,et al.  Morphologic transformation of the thymus in developing zebrafish , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[41]  C. Janeway,et al.  The Toll receptor family and microbial recognition. , 2000, Trends in microbiology.

[42]  Dian‐Chang Zhang,et al.  Cloning, characterization and expression analysis of interleukin-10 from the zebrafish (Danio rerion). , 2005, Journal of biochemistry and molecular biology.

[43]  S. Akira,et al.  Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection1 , 2000, The Journal of Immunology.

[44]  Ruslan Medzhitov,et al.  Toll-like receptors and innate immunity , 2001, Nature Reviews Immunology.

[45]  M. Mishina,et al.  Efficient mutagenesis of zebrafish by a DNA cross-linking agent , 1998, Neuroscience Research.

[46]  R. Jagus,et al.  Characterization of rainbow trout and zebrafish eukaryotic initiation factor 2alpha and its response to endoplasmic reticulum stress and IPNV infection. , 2003, Developmental and comparative immunology.

[47]  M. Kent,et al.  Experimental exposure of zebrafish, Danio rerio (Hamilton), to Mycobacterium marinum and Mycobacterium peregrinum reveals the gastrointestinal tract as the primary route of infection: a potential model for environmental mycobacterial infection. , 2007, Journal of fish diseases.

[48]  Nancy Hopkins,et al.  Identification of 315 genes essential for early zebrafish development. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[49]  S. Agus,et al.  CNS granulomatosis in a child with chronic granulomatous disease. , 2000, British journal of neurosurgery.

[50]  Shizuo Akira,et al.  Toll-like receptor signalling , 2004, Nature Reviews Immunology.

[51]  P. Vignais The superoxide-generating NADPH oxidase: structural aspects and activation mechanism , 2002, Cellular and Molecular Life Sciences CMLS.

[52]  W. Batts,et al.  Susceptibility of zebrafish (Danio rerio) to a model pathogen, spring viremia of carp virus. , 2003, Comparative medicine.

[53]  M. Neely,et al.  Large-Scale Screen Highlights the Importance of Capsule for Virulence in the Zoonotic Pathogen Streptococcus iniae , 2005, Infection and Immunity.

[54]  L. Zon,et al.  Use of the zebrafish system to study primitive and definitive hematopoiesis. , 2005, Annual review of genetics.

[55]  D. Hunnicutt,et al.  Susceptibility of zebra fish Danio rerio to infection by Flavobacterium columnare and F. johnsoniae. , 2007, Diseases of aquatic organisms.

[56]  L. Mcphail,et al.  Coregulation of NADPH oxidase activation and phosphorylation of a 48-kD protein(s) by a cytosolic factor defective in autosomal recessive chronic granulomatous disease. , 1988, The Journal of clinical investigation.

[57]  Chun-Yan Xia,et al.  In vitro effects of recombinant zebrafish IFN on spring viremia of carp virus and infectious hematopoietic necrosis virus. , 2006, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[58]  H. Wolf‐Watz,et al.  Visualisation of zebrafish infection by GFP-labelled Vibrio anguillarum. , 2004, Microbial pathogenesis.

[59]  Zhanjiang Liu,et al.  Constitutive expression of three novel catfish CXC chemokines: homeostatic chemokines in teleost fish. , 2005, Molecular immunology.

[60]  Edwin Cuppen,et al.  Efficient target-selected mutagenesis in zebrafish. , 2003, Genome research.

[61]  Leonard I. Zon,et al.  Organogenesis--Heart and Blood Formation from the Zebrafish Point of View , 2002, Science.

[62]  J. Postlethwait,et al.  A zebrafish sox9 gene required for cartilage morphogenesis. , 2002, Development.

[63]  J. Mullikin,et al.  Methods for reverse genetic screening in zebrafish by resequencing and TILLING. , 2006, Methods.

[64]  M. Neely,et al.  Zebrafish as a model host for streptococcal pathogenesis. , 2004, Acta tropica.

[65]  A. Meijer,et al.  MyD 88 innate immune function in a zebrafish embryo infection model 2 , 2010 .

[66]  A. Estonba,et al.  Innate immune gene expression in individual zebrafish after Listonella anguillarum inoculation. , 2007, Fish & shellfish immunology.

[67]  J. Postlethwait The zebrafish genome in context: ohnologs gone missing. , 2007, Journal of experimental zoology. Part B, Molecular and developmental evolution.

[68]  J. Chluba,et al.  Toll-like receptor gene family and TIR-domain adapters in Danio rerio. , 2004, Molecular immunology.

[69]  M. Neely,et al.  Analysis of the Polysaccharide Capsule of the Systemic Pathogen Streptococcus iniae and Its Implications in Virulence , 2006, Infection and Immunity.

[70]  S. Ekker,et al.  Effective targeted gene ‘knockdown’ in zebrafish , 2000, Nature Genetics.

[71]  L. Ramakrishnan,et al.  Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. , 2002, Immunity.

[72]  L. Tong,et al.  Structural basis for signal transduction by the Toll/interleukin-1 receptor domains , 2000, Nature.

[73]  H. Shu,et al.  Mechanisms of the TRIF-induced Interferon-stimulated Response Element and NF-κB Activation and Apoptosis Pathways* , 2004, Journal of Biological Chemistry.

[74]  G. Flik,et al.  Multiple and highly divergent IL-11 genes in teleost fish , 2005, Immunogenetics.

[75]  M. Ekker,et al.  Gene Expression Pattern , 2022 .

[76]  S. Akira,et al.  Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling1 , 2002, The Journal of Immunology.

[77]  M. Dinauer,et al.  High-level reconstitution of respiratory burst activity in a human X-linked chronic granulomatous disease (X-CGD) cell line and correction of murine X-CGD bone marrow cells by retroviral-mediated gene transfer of human gp91phox. , 1996, Blood.

[78]  K. Anderson,et al.  The Toll gene of drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein , 1988, Cell.

[79]  C. Kimmel,et al.  Zebrafish fgf24 functions with fgf8 to promote posterior mesodermal development , 2003, Development.

[80]  Govinda Rao,et al.  IRF3 mediates a TLR3/TLR4-specific antiviral gene program. , 2002, Immunity.

[81]  A. Look,et al.  Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish , 2006, Journal of leukocyte biology.

[82]  André Catic,et al.  The zebrafish as a model organism to study development of the immune system. , 2003, Advances in immunology.

[83]  P. Jagadeeswaran,et al.  Zebrafish-Mycobacterium marinum model for mycobacterial pathogenesis. , 2003, FEMS microbiology letters.

[84]  M. Neely,et al.  The streptococcal iron uptake (Siu) transporter is required for iron uptake and virulence in a zebrafish infection model. , 2005, Microbiology.

[85]  Ruslan Medzhitov,et al.  Toll-like receptors: linking innate and adaptive immunity. , 2005, Advances in experimental medicine and biology.

[86]  Wilbert Bitter,et al.  Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections , 2003, Cellular microbiology.

[87]  D. Born,et al.  Mycobacterium marinum Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity , 2006, Infection and Immunity.

[88]  A. Kaur,et al.  The evolution of vertebrate Toll-like receptors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[89]  Marc C. Johnson,et al.  Cloning and characterization of an Mx gene and its corresponding promoter from the zebrafish, Danio rerio. , 2004, Developmental and comparative immunology.

[90]  Carol Kim,et al.  Development of a respiratory burst assay using zebrafish kidneys and embryos. , 2004, Journal of immunological methods.

[91]  A. Nairn,et al.  Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[92]  A. Amsterdam,et al.  High-Throughput Selection of Retrovirus Producer Cell Lines Leads to Markedly Improved Efficiency of Germ Line-Transmissible Insertions in Zebra Fish , 2002, Journal of Virology.

[93]  M. Mishina,et al.  Identification of chaperonin CCTγ subunit as a determinant of retinotectal development by whole-genome subtraction cloning from zebrafish no tectal neuron mutant , 2004, Development.

[94]  F. Verbeek,et al.  Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due to Mycobacterium marinum infection. , 2005, Molecular immunology.

[95]  S Akira,et al.  Toll receptor families: structure and function. , 2004, Seminars in immunology.

[96]  J. Curnutte Chronic granulomatous disease: the solving of a clinical riddle at the molecular level. , 1993, Clinical immunology and immunopathology.

[97]  Tak W. Mak,et al.  Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-β , 2004 .

[98]  Nancy Hopkins,et al.  Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. , 2006, Trends in genetics : TIG.

[99]  Daniel R. Caffrey,et al.  LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF , 2003, The Journal of experimental medicine.

[100]  T. Ota,et al.  T cells and the thymus in developing zebrafish. , 2004, Developmental and comparative immunology.

[101]  J. Postlethwait,et al.  Evidence for Evolving Toll-IL-1 Receptor-Containing Adaptor Molecule Function in Vertebrates1 , 2007, The Journal of Immunology.

[102]  J. Pfeifer,et al.  Streptococcus-Zebrafish Model of Bacterial Pathogenesis , 2002, Infection and Immunity.

[103]  A. Oates,et al.  Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish. , 2001, Blood.

[104]  P. Witten,et al.  Pathogenesis and inflammatory response to Edwardsiella tarda infection in the zebrafish. , 2005, Developmental and comparative immunology.

[105]  B. Paw,et al.  Myelopoiesis in the zebrafish, Danio rerio. , 2001, Blood.

[106]  A. Amsterdam,et al.  High-Throughput Selection of Retrovirus Producer Cell Lines Leads to Markedly Improved Efficiency of Germ Line-Transmissible Insertions in Zebra Fish , 2002, Journal of Virology.

[107]  R. M. Smith,et al.  The cytosolic subunit p67phox contains an NADPH-binding site that participates in catalysis by the leukocyte NADPH oxidase. , 1996, The Journal of clinical investigation.

[108]  B. Paw,et al.  The zebrafish spi1 promoter drives myeloid-specific expression in stable transgenic fish. , 2003, Blood.

[109]  L. Zon,et al.  Effects of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus infection on hematopoietic precursors of the zebrafish. , 2000, Blood cells, molecules & diseases.

[110]  G. Elgar Plenty more fish in the sea: comparative and functional genomics using teleost models. , 2004, Briefings in functional genomics & proteomics.

[111]  M. Thelen,et al.  Dancing to the tune of chemokines , 2001, Nature Immunology.

[112]  H. Spaink,et al.  Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish. , 2004, Molecular immunology.

[113]  Marc C. Johnson,et al.  The NV Gene of Snakehead Rhabdovirus (SHRV) Is Not Required for Pathogenesis, and a Heterologous Glycoprotein Can Be Incorporated into the SHRV Envelope , 2004, Journal of Virology.

[114]  J. Fox,et al.  Diagnosis and management of atypical Mycobacterium spp. infections in established laboratory zebrafish (Brachydanio rerio) facilities. , 2000, Comparative medicine.

[115]  A. Ghysen,et al.  Molecular basis of cell migration in the fish lateral line: Role of the chemokine receptor CXCR4 and of its ligand, SDF1 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[116]  L. Steiner,et al.  B cells develop in the zebrafish pancreas , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Paramvir S. Dehal,et al.  Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate , 2005, PLoS biology.

[118]  Yuzuru Suzuki,et al.  Two interleukin (IL)-15 homologues in fish from two distinct origins. , 2006, Molecular immunology.

[119]  A. Figueras,et al.  Zebrafish (Danio rerio) as a model for the study of vaccination against viral haemorrhagic septicemia virus (VHSV). , 2006, Vaccine.

[120]  L. Zon,et al.  The use of zebrafish to understand immunity. , 2004, Immunity.

[121]  Summary Zebrafish fgf 24 functions with fgf 8 to promote posterior mesodermal development , .