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Experimental Models of Intestinal Inflammation: Lessons from Mouse and Zebrafish

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Book cover Molecular Genetics of Inflammatory Bowel Disease

Abstract

Animal models have been instrumental in the study of the cellular and molecular mechanisms underlying human disease, providing the foundation to develop new therapeutic strategies. Although experimental models that completely recapitulate inflammatory bowel disease (IBD) are still missing, key biological processes associated with IBD, such as inflammation, leukocyte trafficking, breach of epithelial barrier integrity, and T cell-mediated damage, can be successfully modeled. Here, we will discuss advantages and disadvantages as well as parallels between human IBD and animal models including established models, such as the murine system, and emerging models, such as zebrafish.

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References

  1. Schwartz S, Rhiner C (2018) Reservoirs for repair? Damage-responsive stem cells and adult tissue regeneration in Drosophila. Int J Dev Biol 62(6–8):465–471

    Article  CAS  PubMed  Google Scholar 

  2. Jiminez JA et al (2015) Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathog 7:29

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lin J, Hackam DJ (2011) Worms, flies and four-legged friends: the applicability of biological models to the understanding of intestinal inflammatory diseases. Dis Model Mech 4(4):447–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pukkila-Worley R, Ausubel FM (2012) Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol 24(1):3–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Felix MA, Duveau F (2012) Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae. BMC Biol 10:59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sim S, Hibberd ML (2016) Caenorhabditis elegans susceptibility to gut Enterococcus faecalis infection is associated with fat metabolism and epithelial junction integrity. BMC Microbiol 16:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gerbaba TK, Green-Harrison L, Buret AG (2017) Modeling host-microbiome interactions in Caenorhabditis elegans. J Nematol 49(4):348–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Apidianakis Y, Rahme LG (2011) Drosophila melanogaster as a model for human intestinal infection and pathology. Dis Model Mech 4(1):21–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jin Y et al (2017) Intestinal stem cell pool regulation in Drosophila. Stem Cell Rep 8(6):1479–1487

    Article  CAS  Google Scholar 

  10. Kietz C, Pollari V, Meinander A (2018) Generating germ-free Drosophila to study gut-microbe interactions: protocol to rear Drosophila under axenic conditions. Curr Protoc Toxicol 77:e52

    Article  PubMed  Google Scholar 

  11. Heys C et al (2018) The effect of gut microbiota elimination in Drosophila melanogaster: a how-to guide for host-microbiota studies. Ecol Evol 8(8):4150–4161

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Howe K et al (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496(7446):498–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brugman S et al (2009) Oxazolone-induced enterocolitis in zebrafish depends on the composition of the intestinal microbiota. Gastroenterology 137(5):1757–1767. e1

    Article  CAS  PubMed  Google Scholar 

  15. Wirtz S et al (2017) Chemically induced mouse models of acute and chronic intestinal inflammation. Nat Protoc 12(7):1295–1309

    Article  CAS  PubMed  Google Scholar 

  16. Powrie F et al (1993) Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol 5(11):1461–1471

    Article  CAS  PubMed  Google Scholar 

  17. Eckmann L (2006) Animal models of inflammatory bowel disease: lessons from enteric infections. Ann N Y Acad Sci 1072:28–38

    Article  CAS  PubMed  Google Scholar 

  18. Mizoguchi A et al (2016) Genetically engineered mouse models for studying inflammatory bowel disease. J Pathol 238(2):205–219

    Article  PubMed  Google Scholar 

  19. Catana CS et al (2018) Comparison of two models of inflammatory bowel disease in rats. Adv Clin Exp Med 27(5):599–607

    Article  PubMed  Google Scholar 

  20. Ekstrom GM (1998) Oxazolone-induced colitis in rats: effects of budesonide, cyclosporin A, and 5-aminosalicylic acid. Scand J Gastroenterol 33(2):174–179

    Article  CAS  PubMed  Google Scholar 

  21. Milia AF et al (2009) HLA-B27 transgenic rat: an animal model mimicking gut and joint involvement in human spondyloarthritides. Ann N Y Acad Sci 1173:570–574

    Article  CAS  PubMed  Google Scholar 

  22. Hammer RE et al (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 63(5):1099–1112

    Article  CAS  PubMed  Google Scholar 

  23. Morales W et al (2011) Acute and chronic histological changes of the small bowel secondary to C. jejuni infection in a rat model for post-infectious IBS. Dig Dis Sci 56(9):2575–2584

    Article  PubMed  Google Scholar 

  24. Crumeyrolle-Arias M et al (2014) Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology 42:207–217

    Article  CAS  PubMed  Google Scholar 

  25. Li D et al (2017) Microbial biogeography and core microbiota of the rat digestive tract. Sci Rep 8:45840

    Article  CAS  PubMed  Google Scholar 

  26. Li S et al (2016) Changes in enteric neurons of small intestine in a rat model of irritable bowel syndrome with diarrhea. J Neurogastroenterol Motil 22(2):310–320

    Article  PubMed  PubMed Central  Google Scholar 

  27. Iwanaga T et al (1994) Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulfate sodium in the guinea pig: some possible mechanisms of cecal ulceration. J Gastroenterol 29(4):430–438

    Article  CAS  PubMed  Google Scholar 

  28. Robinson AM et al (2014) Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 307(11):G1115–G1129

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen TL et al (2015) How informative is the mouse for human gut microbiota research? Dis Model Mech 8(1):1–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shim DH et al (2007) New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies. J Immunol 178(4):2476–2482

    Article  CAS  PubMed  Google Scholar 

  31. Nurgali K et al (2011) Morphological and functional changes in guinea-pig neurons projecting to the ileal mucosa at early stages after inflammatory damage. J Phys 589(Pt 2):325–339

    CAS  Google Scholar 

  32. Xiao Y et al (2017) Early gut microbiota intervention suppresses DSS-induced inflammatory responses by deactivating TLR/NLR signalling in pigs. Sci Rep 7(1):3224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang H et al (2015) Quantitative assessment of inflammation in a porcine acute terminal ileitis model: US with a molecularly targeted contrast agent. Radiology 276(3):809–817

    Article  PubMed  Google Scholar 

  34. Sun J et al (2018) Gene expression profiles of germ-free and conventional piglets from the same litter. Sci Rep 8(1):10745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Splichalova A et al (2018) Preterm life in sterile conditions: a study on preterm, germ-free piglets. Front Immunol 9:220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Van Kruiningen HJ (2016) An infectious pig model of Crohn’s disease. Inflamm Bowel Dis 22(9):2106–2111

    Article  PubMed  Google Scholar 

  37. Leite FL et al (2019) A cell proliferation and inflammatory signature is induced by Lawsonia intracellularis infection in Swine. Mbio 10(1):e01605–e01618

    Google Scholar 

  38. Anthony D et al (1995) The characterization of a rabbit model of inflammatory bowel disease. Int J Exp Pathol 76(3):215–224

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Leonardi I et al (2015) Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits. Int J Exp Pathol 96(3):151–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Velasco-Galilea M et al (2018) Rabbit microbiota changes throughout the intestinal tract. Front Microbiol 9:2144

    Article  PubMed  PubMed Central  Google Scholar 

  41. Arrazuria R et al (2018) Diet induced changes in the microbiota and cell composition of rabbit gut associated lymphoid tissue (GALT). Sci Rep 8(1):14103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen SY et al (2019) Gut microbiota profiling with differential tolerance against the reduced dietary fibre level in rabbit. Sci Rep 9(1):288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sayeed S et al (2008) Beta toxin is essential for the intestinal virulence of Clostridium perfringens type C disease isolate CN3685 in a rabbit ileal loop model. Mol Microbiol 67(1):15–30

    Article  CAS  PubMed  Google Scholar 

  44. Gozalo A et al (2002) Spontaneous terminal ileitis resembling Crohn disease in captive tamarins. J Med Primatol 31(3):142–146

    Article  CAS  PubMed  Google Scholar 

  45. Wood JD et al (2000) Evidence that colitis is initiated by environmental stress and sustained by fecal factors in the cotton-top tamarin (Saguinus oedipus). Dig Dis Sci 45(2):385–393

    Article  CAS  PubMed  Google Scholar 

  46. Ramesh G et al (2005) Visualizing cytokine-secreting cells in situ in the rhesus macaque model of chronic gut inflammation. Clin Diagn Lab Immunol 12(1):192–197

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Yildirim S et al (2010) Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities. PLoS One 5(11):e13963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gardner MB, Luciw PA (2008) Macaque models of human infectious disease. ILAR J 49(2):220–255

    Article  CAS  PubMed  Google Scholar 

  49. Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172(5):2731–2738

    Article  CAS  PubMed  Google Scholar 

  50. Gibbons DL, Spencer J (2011) Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol 4(2):148–157

    Article  CAS  PubMed  Google Scholar 

  51. Zigmond E et al (2014) Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40(5):720–733

    Article  CAS  PubMed  Google Scholar 

  52. Shouval DS et al (2014) Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity 40(5):706–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kotlarz D et al (2012) Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology 143(2):347–355

    Article  CAS  PubMed  Google Scholar 

  54. Wong WM et al (2000) Proliferative populations in intestinal metaplasia: evidence of deregulation in Paneth and goblet cells, but not endocrine cells. J Pathol 190(1):107–113

    Article  CAS  PubMed  Google Scholar 

  55. von Moltke J et al (2016) Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529(7585):221–225

    Article  CAS  Google Scholar 

  56. Schneider C et al (2018) A metabolite-triggered tuft cell-ILC2 circuit drives small intestinal remodeling. Cell 174(2):271–284 e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nadjsombati MS et al (2018) Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49(1):33–41 e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Qu D et al (2015) Ablation of doublecortin-like kinase 1 in the colonic epithelium exacerbates dextran sulfate sodium-induced colitis. PLoS One 10(8):e0134212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Haber AL et al (2017) A single-cell survey of the small intestinal epithelium. Nature 551(7680):333–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Donaldson GP, Lee SM, Mazmanian SK (2016) Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 14(1):20–32

    Article  CAS  PubMed  Google Scholar 

  61. Pabst O (2012) New concepts in the generation and functions of IgA. Nat Rev Immunol 12(12):821–832

    Article  CAS  PubMed  Google Scholar 

  62. Villablanca EJ et al (2011) MyD88 and retinoic acid signaling pathways interact to modulate gastrointestinal activities of dendritic cells. Gastroenterology 141(1):176–185

    Article  CAS  PubMed  Google Scholar 

  63. Johansson-Lindbom B et al (2005) Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med 202(8):1063–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jaensson E et al (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205(9):2139–2149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hart AL et al (2005) Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 129(1):50–65

    Article  CAS  PubMed  Google Scholar 

  66. Czarnewski P et al (2017) Retinoic acid and its role in modulating intestinal innate immunity. Nutrients 9(1):68

    Google Scholar 

  67. Villablanca EJ (2013) Retinoic acid-producing DCs and gut-tropic FOXP3 regulatory T cells in the induction of oral tolerance. Oncoimmunology 2(2):e22987

    Article  PubMed  PubMed Central  Google Scholar 

  68. Feagan BG et al (2013) Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 369(8):699–710

    Article  CAS  PubMed  Google Scholar 

  69. Ananthakrishnan AN et al (2012) Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med 156(5):350–359

    Article  PubMed  PubMed Central  Google Scholar 

  70. Morris GP et al (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96(3):795–803

    Article  CAS  PubMed  Google Scholar 

  71. Neurath MF et al (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182(5):1281–1290

    Article  CAS  PubMed  Google Scholar 

  72. Fiorucci S et al (2002) Importance of innate immunity and collagen binding integrin alpha1beta1 in TNBS-induced colitis. Immunity 17(6):769–780

    Article  CAS  PubMed  Google Scholar 

  73. Elson CO et al (1996) Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 157(5):2174–2185

    CAS  PubMed  Google Scholar 

  74. Dohi T et al (1999) Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses. J Exp Med 189(8):1169–1180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yang Z et al (2007) NOD2 transgenic mice exhibit enhanced MDP-mediated down-regulation of TLR2 responses and resistance to colitis induction. Gastroenterology 133(5):1510–1521

    Article  CAS  PubMed  Google Scholar 

  76. Barreau F et al (2007) CARD15/NOD2 is required for Peyer’s patches homeostasis in mice. PLoS One 2(6):e523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mannon PJ et al (2004) Anti-interleukin-12 antibody for active Crohn’s disease. N Engl J Med 351(20):2069–2079

    Article  CAS  PubMed  Google Scholar 

  78. Feagan BG et al (2016) Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 375(20):1946–1960

    Article  CAS  PubMed  Google Scholar 

  79. Okayasu I et al (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98(3):694–702

    Article  CAS  PubMed  Google Scholar 

  80. Laroui H et al (2012) Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon. PLoS One 7(3):e32084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wirtz S et al (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2(3):541–546

    Article  CAS  PubMed  Google Scholar 

  82. Dieleman LA et al (1994) Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107(6):1643–1652

    Article  CAS  PubMed  Google Scholar 

  83. Mahler M et al (1998) Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Phys 274(3 Pt 1):G544–G551

    CAS  Google Scholar 

  84. Hudcovic T et al (2001) The role of microflora in the development of intestinal inflammation: acute and chronic colitis induced by dextran sulfate in germ-free and conventionally reared immunocompetent and immunodeficient mice. Folia Microbiol (Praha) 46(6):565–572

    Article  CAS  Google Scholar 

  85. Hernandez-Chirlaque C et al (2016) Germ-free and antibiotic-treated mice are highly susceptible to epithelial injury in DSS colitis. J Crohns Colitis 10(11):1324–1335

    Article  PubMed  Google Scholar 

  86. Kitajima S et al (2001) Dextran sodium sulfate-induced colitis in germ-free IQI/Jic mice. Exp Anim 50(5):387–395

    Article  CAS  PubMed  Google Scholar 

  87. Mizoguchi A (2012) Animal models of inflammatory bowel disease. Prog Mol Biol Transl Sci 105:263–320

    Article  CAS  PubMed  Google Scholar 

  88. Boirivant M et al (1998) Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med 188(10):1929–1939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Heller F et al (2002) Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17(5):629–638

    Article  CAS  PubMed  Google Scholar 

  90. Iijima H et al (2004) Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J Exp Med 199(4):471–482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Olszak T et al (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336(6080):489–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Gerlach K et al (2014) TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol 15(7):676–686

    Article  CAS  PubMed  Google Scholar 

  93. Ni J et al (2017) Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol 14(10):573–584

    Article  PubMed  PubMed Central  Google Scholar 

  94. Schultz BM et al (2017) A potential role of Salmonella infection in the onset of inflammatory bowel diseases. Front Immunol 8:191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Barthel M et al (2003) Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun 71(5):2839–2858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Grassl GA et al (2008) Chronic enteric salmonella infection in mice leads to severe and persistent intestinal fibrosis. Gastroenterology 134(3):768–780

    Article  CAS  PubMed  Google Scholar 

  97. Low D, Nguyen DD, Mizoguchi E (2013) Animal models of ulcerative colitis and their application in drug research. Drug Des Devel Ther 7:1341–1357

    PubMed  PubMed Central  Google Scholar 

  98. Hess J et al (1996) Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-alpha beta cells and IFN-gamma in bacterial clearance independent of intracellular location. J Immunol 156(9):3321–3326

    CAS  PubMed  Google Scholar 

  99. Ravindran R et al (2005) Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. J Immunol 175(7):4603–4610

    Article  CAS  PubMed  Google Scholar 

  100. Tam MA et al (2008) Early cellular responses to Salmonella infection: dendritic cells, monocytes, and more. Immunol Rev 225:140–162

    Article  CAS  PubMed  Google Scholar 

  101. Conway KL et al (2013) Atg16l1 is required for autophagy in intestinal epithelial cells and protection of mice from Salmonella infection. Gastroenterology 145(6):1347–1357

    Article  CAS  PubMed  Google Scholar 

  102. Spalinger MR, Rogler G, Scharl M (2014) Crohn’s disease: loss of tolerance or a disorder of autophagy? Dig Dis 32(4):370–377

    Article  PubMed  Google Scholar 

  103. Higgins LM et al (1999) Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease. Infect Immun 67(6):3031–3039

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Crepin VF et al (2016) Citrobacter rodentium mouse model of bacterial infection. Nat Protoc 11(10):1851–1876

    Article  CAS  PubMed  Google Scholar 

  105. Mundy R et al (2005) Citrobacter rodentium of mice and man. Cell Microbiol 7(12):1697–1706

    Article  CAS  PubMed  Google Scholar 

  106. Ghaem-Maghami M et al (2001) Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium. Infect Immun 69(9):5597–5605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Deng W et al (2004) Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proc Natl Acad Sci U S A 101(10):3597–3602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zheng Y et al (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14(3):282–289

    Article  CAS  PubMed  Google Scholar 

  109. Zindl CL et al (2013) IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc Natl Acad Sci U S A 110(31):12768–12773

    Article  PubMed  PubMed Central  Google Scholar 

  110. Sokol H et al (2017) Fungal microbiota dysbiosis in IBD. Gut 66(6):1039–1048

    Article  CAS  PubMed  Google Scholar 

  111. Jawhara S et al (2008) Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J Infect Dis 197(7):972–980

    Article  CAS  PubMed  Google Scholar 

  112. Jawhara S, Poulain D (2007) Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis. Med Mycol 45(8):691–700

    Article  CAS  PubMed  Google Scholar 

  113. Sovran B et al (2018) Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome 6(1):152

    Article  PubMed  PubMed Central  Google Scholar 

  114. Iliev ID et al (2012) Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336(6086):1314–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Leonardi I et al (2018) CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi. Science 359(6372):232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Norman JM et al (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160(3):447–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lencioni KC et al (2008) Murine norovirus: an intercurrent variable in a mouse model of bacteria-induced inflammatory bowel disease. Comp Med 58(6):522–533

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Cadwell K et al (2010) Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141(7):1135–1145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Brunson JL, Becker F, Stokes KY (2015) The impact of primary and persistent cytomegalovirus infection on the progression of acute colitis in a murine model. Pathophysiology 22(1):31–37

    Article  CAS  PubMed  Google Scholar 

  120. Liesenfeld O et al (1996) Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 184(2):597–607

    Article  CAS  PubMed  Google Scholar 

  121. Oldenhove G et al (2009) Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31(5):772–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Chudnovskiy A et al (2016) Host-protozoan interactions protect from mucosal infections through activation of the inflammasome. Cell 167(2):444–456 e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Escalante NK et al (2016) The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility. J Exp Med 213(13):2841–2850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Howitt MR et al (2016) Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351(6279):1329–1333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. de Lange KM et al (2017) Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49(2):256–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Jostins L et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Agus A et al (2016) Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci Rep 6:19032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kuhn R et al (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274

    Article  CAS  PubMed  Google Scholar 

  129. Davidson NJ et al (1996) T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184(1):241–251

    Article  CAS  PubMed  Google Scholar 

  130. Sheikh SZ et al (2010) Cutting edge: IFN-gamma is a negative regulator of IL-23 in murine macrophages and experimental colitis. J Immunol 184(8):4069–4073

    Article  CAS  PubMed  Google Scholar 

  131. Kontoyiannis D et al (1999) Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10(3):387–398

    Article  CAS  PubMed  Google Scholar 

  132. Rothfuss KS, Stange EF, Herrlinger KR (2006) Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol 12(30):4819–4831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vavricka SR et al (2015) Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis 21(8):1982–1992

    Article  PubMed  Google Scholar 

  134. Kontoyiannis D et al (2002) Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn’s-like inflammatory bowel disease. J Exp Med 196(12):1563–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Apostolaki M et al (2008) Role of beta7 integrin and the chemokine/chemokine receptor pair CCL25/CCR9 in modeled TNF-dependent Crohn’s disease. Gastroenterology 134(7):2025–2035

    Article  CAS  PubMed  Google Scholar 

  136. Dupuis-Girod S et al (2003) Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics 111(5 Pt 1):e622–e627

    Article  PubMed  Google Scholar 

  137. Pollitt AY, Insall RH (2009) WASP and SCAR/WAVE proteins: the drivers of actin assembly. J Cell Sci 122(Pt 15):2575–2578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Nguyen DD et al (2007) Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein. Gastroenterology 133(4):1188–1197

    Article  CAS  PubMed  Google Scholar 

  139. Snapper SB et al (1998) Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9(1):81–91

    Article  CAS  PubMed  Google Scholar 

  140. Maillard MH et al (2007) The Wiskott-Aldrich syndrome protein is required for the function of CD4(+)CD25(+)Foxp3(+) regulatory T cells. J Exp Med 204(2):381–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Hugot JP et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603

    Article  CAS  PubMed  Google Scholar 

  142. Ogura Y et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837):603–606

    Article  CAS  PubMed  Google Scholar 

  143. Watanabe T et al (2004) NOD2 is a negative regulator of toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5(8):800–808

    Article  CAS  PubMed  Google Scholar 

  144. Maul J et al (2005) Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 128(7):1868–1878

    Article  CAS  PubMed  Google Scholar 

  145. Boden EK, Snapper SB (2008) Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol 24(6):733–741

    Article  PubMed  Google Scholar 

  146. Leach MW et al (1996) Inflammatory bowel disease in C.B-17 scid mice reconstituted with the CD45RBhigh subset of CD4+ T cells. Am J Pathol 148(5):1503–1515

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Mottet C, Uhlig HH, Powrie F (2003) Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 170(8):3939–3943

    Article  CAS  PubMed  Google Scholar 

  148. Powrie F et al (1994) Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1(7):553–562

    Article  CAS  PubMed  Google Scholar 

  149. Sorini C et al (2018) Commensal bacteria-specific CD4(+) T cell responses in health and disease. Front Immunol 9:2667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Feng T et al (2011) Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol 186(11):6313–6318

    Article  CAS  PubMed  Google Scholar 

  151. Liu Z et al (1999) Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production. J Immunol 163(7):4049–4057

    CAS  PubMed  Google Scholar 

  152. Battaglia E et al (1999) Expression of CD40 and its ligand, CD40L, in intestinal lesions of Crohn’s disease. Am J Gastroenterol 94(11):3279–3284

    Article  CAS  PubMed  Google Scholar 

  153. Polese L et al (2002) The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation. Eur J Gastroenterol Hepatol 14(3):237–241

    Article  PubMed  Google Scholar 

  154. Uhlig HH et al (2006) Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25(2):309–318

    Article  CAS  PubMed  Google Scholar 

  155. Vonarbourg C et al (2010) Regulated expression of nuclear receptor RORgammat confers distinct functional fates to NK cell receptor-expressing RORgammat(+) innate lymphocytes. Immunity 33(5):736–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discovery 14(10):721–731

    Article  CAS  PubMed  Google Scholar 

  157. Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discovery 4(1):35–44

    Article  CAS  PubMed  Google Scholar 

  158. 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 

  159. Herbomel P, Thisse B, Thisse C (1999) Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development 126(17):3735–3745

    CAS  PubMed  Google Scholar 

  160. Lieschke GJ et al (2001) Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish. Blood 98(10):3087–3096

    Article  CAS  PubMed  Google Scholar 

  161. Dobson JT et al (2008) Carboxypeptidase A5 identifies a novel mast cell lineage in the zebrafish providing new insight into mast cell fate determination. Blood 112(7):2969–2972

    Article  CAS  PubMed  Google Scholar 

  162. Lugo-Villarino G et al (2010) Identification of dendritic antigen-presenting cells in the zebrafish. Proc Natl Acad Sci U S A 107(36):15850–15855

    Article  PubMed  PubMed Central  Google Scholar 

  163. Page DM et al (2013) An evolutionarily conserved program of B-cell development and activation in zebrafish. Blood 122(8):e1–e11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Willett CE et al (1997) Expression of zebrafish rag genes during early development identifies the thymus. Dev Biol 182(2):331–341

    Article  CAS  PubMed  Google Scholar 

  165. Tang Q et al (2017) Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing. J Exp Med 214(10):2875–2887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Hernandez PP et al (2018) Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Sci Immunol 3(29):eaau5265

    Google Scholar 

  167. 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 

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

    Article  CAS  PubMed  Google Scholar 

  169. 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 

  170. Jijon HB et al (2018) Intestinal epithelial cell-specific RARalpha depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system. Mucosal Immunol 11(3):703–715

    Article  CAS  PubMed  Google Scholar 

  171. Langenau DM et al (2004) In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish. Proc Natl Acad Sci U S A 101(19):7369–7374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Trede NS et al (2004) The use of zebrafish to understand immunity. Immunity 20(4):367–379

    Article  CAS  PubMed  Google Scholar 

  173. Danilova N et al (2005) The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6(3):295–302

    Article  CAS  PubMed  Google Scholar 

  174. Zhang YA et al (2010) IgT, a primitive immunoglobulin class specialized in mucosal immunity. Nat Immunol 11(9):827–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Wallace KN, Pack M (2003) Unique and conserved aspects of gut development in zebrafish. Dev Biol 255(1):12–29

    Article  CAS  PubMed  Google Scholar 

  176. Brugman S (2016) The zebrafish as a model to study intestinal inflammation. Dev Comp Immunol 64:82–92

    Article  CAS  PubMed  Google Scholar 

  177. 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 

  178. 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 

  179. Antoniou E et al (2016) The TNBS-induced colitis animal model: an overview. Ann Med Surg (Lond) 11:9–15

    Article  Google Scholar 

  180. Mowat C et al (2011) Guidelines for the management of inflammatory bowel disease in adults. Gut 60(5):571–607

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Annese V et al (2005) Erythrocytes-mediated delivery of dexamethasone in steroid-dependent IBD patients-a pilot uncontrolled study. Am J Gastroenterol 100(6):1370–1375

    Article  CAS  PubMed  Google Scholar 

  183. Oehlers SH et al (2017) A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. FEBS J 284(3):402–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Kawakami K, Shima A, Kawakami N (2000) Identification of a functional transposase of the Tol2 element, an Ac-like element from the Japanese medaka fish, and its transposition in the zebrafish germ lineage. Proc Natl Acad Sci U S A 97(21):11403–11408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Meyer A, Schartl M (1999) Gene and genome duplications in vertebrates: the one-to-four (-to-eight in fish) rule and the evolution of novel gene functions. Curr Opin Cell Biol 11(6):699–704

    Article  CAS  PubMed  Google Scholar 

  186. Doyon Y et al (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26(6):702–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Hwang WY et al (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31(3):227–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Marjoram L et al (2015) Epigenetic control of intestinal barrier function and inflammation in zebrafish. Proc Natl Acad Sci U S A 112(9):2770–2775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Lassen KG et al (2014) Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc Natl Acad Sci U S A 111(21):7741–7746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Pott J, Kabat AM, Maloy KJ (2018) Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice. Cell Host Microbe 23(2):191–202. e4

    Article  CAS  PubMed  Google Scholar 

  191. Zhao S et al (2018) Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish. Nat Commun 9(1):2639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Hou JK, Abraham B, El-Serag H (2011) Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 106(4):563–573

    Article  CAS  PubMed  Google Scholar 

  193. Martinez-Medina M et al (2014) Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut 63(1):116–124

    Article  CAS  PubMed  Google Scholar 

  194. Progatzky F et al (2014) Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation. Nat Commun 5:5864

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. El-Brolosy MA, Stainier DYR (2017) Genetic compensation: a phenomenon in search of mechanisms. PLos Genet 13(7):e1006780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Oscar E. Diaz and Rodrigo A. Morales equally contributed.

Authors and Affiliations

  1. Department of Medicine, Solna, Science for Life Laboratory, Karolinska Institute and University Hospital, Stockholm, Sweden

    Oscar E. Diaz, Rodrigo A. Morales, Srustidhar Das & Eduardo J. Villablanca

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  1. Oscar E. Diaz
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  2. Rodrigo A. Morales
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  3. Srustidhar Das
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  4. Eduardo J. Villablanca
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Correspondence to Eduardo J. Villablanca .

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Editors and Affiliations

  1. Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden

    Charlotte Hedin

  2. Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada

    John D. Rioux

  3. School of Biological Sciences, Monash University, Clayton, VIC, Australia

    Mauro D'Amato

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Diaz, O.E., Morales, R.A., Das, S., Villablanca, E.J. (2019). Experimental Models of Intestinal Inflammation: Lessons from Mouse and Zebrafish. In: Hedin, C., Rioux, J., D'Amato, M. (eds) Molecular Genetics of Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-28703-0_3

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