Skip to main content

Advertisement

SpringerLink
Log in

Infection, Inflammation and Healing in Zebrafish: Intestinal Inflammation

  • Zebrafish as a Model for Pathobiology (Wolfram Goessling, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, contribute to significant morbidity and mortality globally. Despite an increase in incidence, IBD onset is still poorly understood. Mouse models of IBD recapitulate several aspects of human disease, but limited accessibility for live imaging and the lack of forward genetics highlight the need for new model systems for disease onset characterization. Zebrafish represent a powerful platform to model IBD using forward and reverse genetics, live imaging of transgenic lines, and physiological assays. In this review, we address current models of IBD in zebrafish and newly developed reagents available for future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3(7):390–407

    Article  CAS  PubMed  Google Scholar 

  2. Wirtz S, Neurath MF (2007) Mouse models of inflammatory bowel disease. Adv Drug Deliv Rev 59(11):1073–1083

    Article  CAS  PubMed  Google Scholar 

  3. Paquette CE et al (2013) A retrospective study of the prevalence and classification of intestinal neoplasia in zebrafish (Danio rerio). Zebrafish 10(2):228–236

    Article  PubMed Central  PubMed  Google Scholar 

  4. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298(5601):2188–2290

    Article  CAS  PubMed  Google Scholar 

  5. Gemberling M et al (2013) The zebrafish as a model for complex tissue regeneration. Trends Genet 29(11):611–620

    Article  CAS  PubMed  Google Scholar 

  6. Ingham PW (2009) The power of the zebrafish for disease analysis. Hum Mol Genet 18(R1):R107–R112

    Article  CAS  PubMed  Google Scholar 

  7. • Ryan S et al (2013) Rapid identification of kidney cyst mutations by whole exome sequencing in zebrafish. Development 140(21):4445–4451. This article provides a comprehensive approach to sequencing mutants identified from forward genetic screens using the newly developed platform SNPTrack

  8. •• Schulte-Merker S, Stainier DY (2014) Out with the old, in with the new: reassessing morpholino knockdowns in light of genome editing technology. Development 141(16):3103–3104. This review describes the caveats of morpholino-based knockdown experiments and highlights the strengths of TALEN and CRISPR approaches

  9. Ng AN et al (2005) Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis. Dev Biol 286(1):114–135

    Article  CAS  PubMed  Google Scholar 

  10. Wallace KN et al (2005) Intestinal growth and differentiation in zebrafish. Mech Dev 122(2):157–173

    Article  CAS  PubMed  Google Scholar 

  11. Feitsma H, Cuppen E (2008) Zebrafish as a cancer model. Mol Cancer Res 6(5):685–694

    Article  CAS  PubMed  Google Scholar 

  12. Goldsmith JR, Jobin C (2012) Think small: zebrafish as a model system of human pathology. J Biomed Biotechnol 2012:817341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Strober W, Fuss I, Mannon P (2007) The fundamental basis of inflammatory bowel disease. J Clin Invest 117(3):514–521

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9(11):799–809

    Article  CAS  PubMed  Google Scholar 

  15. Lam SH et al (2004) Development and maturation of the immune system in zebrafish, Danio rerio: a gene expression profiling, in situ hybridization and immunological study. Dev Comp Immunol 28(1):9–28

    Article  CAS  PubMed  Google Scholar 

  16. Oehlers SH et al (2013) Chemically induced intestinal damage models in zebrafish larvae. Zebrafish 10(2):184–193

    Article  CAS  PubMed  Google Scholar 

  17. • Cocchiaro JL, Rawls JF (2013) Microgavage of zebrafish larvae. J Vis Exp (72):e4434. This article is a thorough methods paper that provides a written protocol and a visual demonstration of microgavage

  18. Fleming A, Jankowski J, Goldsmith P (2010) In vivo analysis of gut function and disease changes in a zebrafish larvae model of inflammatory bowel disease: a feasibility study. Inflamm Bowel Dis 16(7):1162–1172

    Article  PubMed  Google Scholar 

  19. He Q et al (2013) Microbial fingerprinting detects intestinal microbiota dysbiosis in Zebrafish models with chemically-induced enterocolitis. BMC Microbiol 13:289

    Article  PubMed Central  PubMed  Google Scholar 

  20. Oehlers SH et al (2011) A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents. Dev Dyn 240(1):288–298

    Article  CAS  PubMed  Google Scholar 

  21. Crawford KC et al (2011) Zebrafish heat shock protein a4 genes in the intestinal epithelium are up-regulated during inflammation. Genesis 49(12):905–911

    Article  CAS  PubMed  Google Scholar 

  22. Geiger BM et al (2013) Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish. PLoS One 8(12):e83194

    Article  PubMed Central  PubMed  Google Scholar 

  23. Brugman S et al (2009) Oxazolone-induced enterocolitis in zebrafish depends on the composition of the intestinal microbiota. Gastroenterology 137(5):1757–1767

    Article  CAS  PubMed  Google Scholar 

  24. Oehlers SH et al (2012) Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis. Dis Model Mech 5(4):457–467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Goldsmith JR et al (2013) Glafenine-induced intestinal injury in zebrafish is ameliorated by mu-opioid signaling via enhancement of Atf6-dependent cellular stress responses. Dis Model Mech 6(1):146–159

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Bates JM et al (2007) Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2(6):371–382

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Novoa B et al (2009) LPS response and tolerance in the zebrafish (Danio rerio). Fish Shellfish Immunol 26(2):326–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. •• Progatzky F et al (2014) Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation. Nat Commun 5:5864. This article demonstrates the importance of diet in intestinal inflammation and will be of great interest to intestinal inflammation researchers

  29. Augustine S et al (2015) Effects of chronic exposure to environmentally relevant concentrations of waterborne depleted uranium on the digestive tract of zebrafish, Danio rerio. J Environ Radioact 142C:45–53

    Article  Google Scholar 

  30. Delco F, Sonnenberg A (1998) Military history of patients with inflammatory bowel disease: an epidemiological study among U.S. veterans. Am J Gastroenterol 93(9):1457–1462

    Article  CAS  PubMed  Google Scholar 

  31. Sonnenberg A, Richardson PA, Abraham NS (2009) Hospitalizations for inflammatory bowel disease among US military veterans 1975-2006. Dig Dis Sci 54(8):1740–1745

    Article  PubMed  Google Scholar 

  32. Hedrera MI et al (2013) Soybean meal induces intestinal inflammation in zebrafish larvae. PLoS ONE 8(7):e69983

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. •• Marjoram L et al (2015) Epigenetic control of intestinal barrier function and inflammation in zebrafish. Proc Natl Acad Sci USA 112(9):2770–2775. This article provides the first comprehensive genetic model of IBD in zebrafish. A new inflammation-responsive transgenic line, TgBAC(tnfa:GFP) is reported

  34. • Scarpa M, Stylianou E (2012) Epigenetics: Concepts and relevance to IBD pathogenesis. Inflamm Bowel Dis 18(10):1982–1996. This review details the role that epigenetics may play in IBD onset and progression

  35. Pham LN et al (2008) Methods for generating and colonizing gnotobiotic zebrafish. Nat Protoc 3(12):1862–1875

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Bates JM et al (2006) Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 297(2):374–386

    Article  CAS  PubMed  Google Scholar 

  37. Jemielita M et al (2014) Spatial and temporal features of the growth of a bacterial species colonizing the zebrafish gut. MBio 5(6):e01751

    Article  PubMed Central  PubMed  Google Scholar 

  38. Russo P et al (2015) Zebrafish gut colonization by mCherry-labelled lactic acid bacteria. Appl Microbiol Biotechnol 99(8):3479–3490

    Article  CAS  PubMed  Google Scholar 

  39. Hall C et al (2007) The zebrafish lysozyme C promoter drives myeloid-specific expression in transgenic fish. BMC Dev Biol 7:42

    Article  PubMed Central  PubMed  Google Scholar 

  40. Flores MV et al (2010) Dual oxidase in the intestinal epithelium of zebrafish larvae has anti-bacterial properties. Biochem Biophys Res Commun 400(1):164–168

    Article  CAS  PubMed  Google Scholar 

  41. Oehlers SH et al (2011) The inflammatory bowel disease (IBD) susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish. Dis Model Mech 4(6):832–841

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Rendueles O et al (2012) A new zebrafish model of oro-intestinal pathogen colonization reveals a key role for adhesion in protection by probiotic bacteria. PLoS Pathog 8(7):e1002815

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Liu X et al (2014) Role of intestinal inflammation in predisposition of Edwardsiella tarda infection in zebrafish (Danio rerio). Fish Shellfish Immunol 41(2):271–278

    Article  PubMed  Google Scholar 

  44. Kanther M et al (2011) Microbial colonization induces dynamic temporal and spatial patterns of NF-kappaB activation in the zebrafish digestive tract. Gastroenterology 141(1):197–207

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Yang CT et al (2012) Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe 12(3):301–312

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Renshaw SA et al (2006) A transgenic zebrafish model of neutrophilic inflammation. Blood 108(13):3976–3978

    Article  CAS  PubMed  Google Scholar 

  47. Ellett F et al (2011) mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish. Blood 117(4):e49–e56

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Gray C et al (2011) Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish. Thromb Haemost 105(5):811–819

    Article  CAS  PubMed  Google Scholar 

  49. Boglev Y et al (2013) Autophagy induction is a Tor- and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis. PLoS Genet 9(2):e1003279

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Chen JN et al (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development 123:293–302

    CAS  PubMed  Google Scholar 

  51. de Jong-Curtain TA et al (2009) Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish. Gastroenterology 136(3):902–911

    Article  PubMed Central  PubMed  Google Scholar 

  52. Jones SA, Mills KH, Harris J (2013) Autophagy and inflammatory diseases. Immunol Cell Biol 91(3):250–258

    Article  CAS  PubMed  Google Scholar 

  53. Alvers AL et al (2014) Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling. Development 141(5):1110–1119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Rodriguez-Fraticelli AE et al (2015) Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs. Nat Cell Biol 17(3):241–250

    Article  CAS  PubMed  Google Scholar 

  55. Bassi A, Schmid B, Huisken J (2015) Optical tomography complements light sheet microscopy for in toto imaging of zebrafish development. Development 142(5):1016–1020

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We apologize to those, whose work we could not discuss due to space restrictions. We thank Ashley Alvers for critical reading of the manuscript. L.M. was supported by an NIH National Research Service Award (F32-DK098885-01A1) and M.B. was supported by a Grand Challenges Explorations Grant OPP1108132 from the Bill & Melinda Gates Foundation.

Author information

Authors and Affiliations

  1. Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA

    Lindsay Marjoram & Michel Bagnat

Authors
  1. Lindsay Marjoram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michel Bagnat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lindsay Marjoram.

Additional information

This article is part of the Topical Collection on Zebrafish as a Model for Pathobiology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marjoram, L., Bagnat, M. Infection, Inflammation and Healing in Zebrafish: Intestinal Inflammation. Curr Pathobiol Rep 3, 147–153 (2015). https://doi.org/10.1007/s40139-015-0079-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40139-015-0079-x

Keywords

Search

Navigation