Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota

Seminars in Immunology

Volumn 19, Issue 2, 2007, Pages 59-69

  Smith, Karen ^a   McCoy, Kathy D ^a   Macpherson, Andrew J ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Axenic; Commensal bacteria; Deriving and maintaining germ free animals; Germ free; Gnotobiotic; Host commensal mutualism; Inflammatory bowel disease; Mucosal immune system; Schaedler flora

Indexed keywords

BACTERIAL COLONIZATION; COMMENSAL; ENTERITIS; GERMFREE ANIMAL; GNOTOBIOTICS; HUMAN; IMMUNE SYSTEM; INTESTINE FLORA; MICROBIOLOGY; NONHUMAN; REVIEW; SPECTROSCOPY; SYMBIOSIS;

ANIMALS; BACTERIA; GERM-FREE LIFE; IMMUNITY, MUCOSAL; INTESTINAL MUCOSA; INTESTINES; MAMMALS; MODELS, ANIMAL; SYMBIOSIS;

EID: 34249284197     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.smim.2006.10.002     Document Type: Review

References (163)

1. Schaedler R.W., Dubos R., and Costello R. Association of germfree mice with bacteria isolated from normal mice. J Exp Med 122 (1965) 77-83
2. Dubos R., and Schaedler R.W. The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections. J Exp Med 111 (1960) 407-411
3. Orcutt R.P., Gianni F.J., and Judge R.J. Development of an 'Altered Schaedler flora' for NCI gnotobiotic rodents. Microecol Ther 17 (1987) 59
4. Dewhirst F.E., Chien C.C., Paster B.J., Ericson R.L., Orcutt R.P., Schauer D.B., et al. Phylogeny of the defined murine microbiota: altered Schaedler flora. Appl Environ Microbiol 65 (1999) 3287-3292
5. Baker D.G. Natural pathogens of laboratory mice, rats, and rabbits and their effects on research. Clin Microbiol Rev 11 (1998) 231-266
6. Billroth T. Untersuchungen über die Vegetationsformen von Coccobacteria septica. Berlin; 1874.
7. Escherich T. Die Darmbakterien des Neugeborenen und Säuglings. Fortschritte der Medizin 3 (1885) 515-547
8. Cushing H., and Livingood L.E. Experimental and surgical notes upon the bacteriology of the upper portion of the alimentary canal, with observations on the establishment there of an amicrobic state as a preliminary to operative procedures on the stomach and small intestine. John's Hopkins Hospital Reports 9 (1900) 543-549
9. Pasteur L. Observations relatives a la note de M. Duclaux. Compt Rend 100 (1885) 69
10. Cohendy M. Experiences sur la vie sans microbes. Compt Rend 154 (1912) 533-536
11. Cohendy M. Experiences sur la vie sans microbes, élevage aseptique de cobages. Compt Rend 158 (1914) 1283-1284
12. Glimstedt G. Bakterienfrei Meerschweinchen. Aufzucht, Lebensfähigkeit und Wachstum, nebst Untersuchung über das lymphatische Gewebe. Acta Pathol Microbiol Scand Suppl 30 (1936) 1-295
13. Reyniers J.A. The pure culture concept and gnotobiotics. Ann N Y Acad Sci 78 (1959) 3-16
14. Gustafsson B.E. Vitamin K deficiency in germfree rats. Ann N Y Acad Sci 78 (1959) 166-174
15. Ogura Y., Bonen D.K., Inohara N., Nicolae D.L., Chen F.F., Ramos R., et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411 (2001) 603-606
16. Hugot J.P., Chamaillard M., Zouali H., Lesage S., Cezard J.P., Belaiche J., et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411 (2001) 599-603
17. Hampe J., Cuthbert A., Croucher P.J.P., Mirza M.M., Mascheretti S., Fisher S., et al. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357 (2001) 1925-1928
18. Inohara N., and Nunez G. NODs, intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 3 (2003) 371-382
19. Girardin S.E., Boneca I.G., Viala J., Chamaillard M., Labigne A., Thomas G., et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278 (2003) 8869-8872
20. Kuhn R., Lohler J., Rennick D., Rajewsky K., and Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75 (1993) 263-274
21. Sadlack B., Merz H., Schorle H., Schimpl A., Feller A.C., and Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75 (1993) 253-261
22. Mombaerts P., Mizoguchi E., Grusby M.J., Glimcher L.H., Bhan A.K., and Tonegawa S. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75 (1993) 274-282
23. Mueller C., and Macpherson A.J. Layers of mutualism with commensal bacteria protect us from intestinal inflammation. Gut 55 (2006) 276-284
24. Parrott D.M., and Ferguson A. Selective migration of lymphocytes within the mouse small intestine. Immunology 26 (1974) 571-588
25. Rhee K.J., Sethupathi P., Driks A., Lanning D.K., and Knight K.L. Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 172 (2004) 1118-1124
26. Helgeland L., Vaage J.T., Rolstad B., Halstensen T.S., Midtvedt T., and Brandtzaeg P. Regional phenotypic specialization of intraepithelial lymphocytes in the rat intestine does not depend on microbial colonization. Scand J Immunol 46 (1997) 349-357
27. Helgeland L., Vaage J.T., Rolstad B., Midtvedt T., and Brandtzaeg P. Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine. Immunology 89 (1996) 494-501
28. Guy-Grand D., Griscelli C., and Vassalli P. The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med 148 (1978) 1661-1677
29. Hooper L.V., and Gordon J.I. Commensal host-bacterial relationships in the gut. Science 292 (2001) 1115-1118
30. Hooper L.V., Stappenbeck T.S., Hong C.V., and Gordon J.I. Angiogenins, a new class of microbicidal proteins involved in innate immunity. Nat Immunol 4 (2003) 269-273
31. Stappenbeck T.S., Hooper L.V., and Gordon J.I. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99 (2002) 15451-15455
32. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101 (2004) 15718-15723
33. Bauer H., Horowitz R.E., Levenson S.M., and Popper H. The response of lymphatic tissue to the microbial flora. Studies on germfree mice. Am J Path 42 (1963) 471-479
34. Manolios N., Geczy C.L., and Schrieber L. High endothelial venule morphology and function are inducible in germ-free mice: a possible role for interferon-gamma. Cell Immunol 117 (1988) 136-151
35. Macpherson A.J., Gatto D., Sainsbury E., Harriman G.R., Hengartner H., and Zinkernagel R.M. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288 (2000) 2222-2226
36. Konrad A., Cong Y., Duck W., Borlaza R., and Elson C.O. Tight mucosal compartmentation of the murine immune response to antigens of the enteric microbiota. Gastroenterology 130 (2006) 2050-2059
37. Mazmanian S.K., Liu C.H., Tzianabos A.O., and Kasper D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122 (2005) 107-118
38. Wostmann B.S. The germfree animal in nutritional studies. Annu Rev Nutr 1 (1981) 257-279
39. Wostmann B.S., and Knight P.L. Antagonism between vitamins A and K in the germfree rat. J Nutr 87 (1965) 155-160
40. Sumi Y., Miyakawa M., Kanzaki M., and Kotake Y. Vitamin B-6 deficiency in germfree rats. J Nutr 107 (1977) 1707-1714
41. Levenson S.M., and Tennant B. Some metabolic and nutritional studies with germfree animals. Fed Proc 22 (1963) 109-119
42. Gordon H.A. Is the germ-free animal normal?. In: Coates M.E. (Ed). The germ free animal in research (1968), Academic Press, London and New York 127-150
43. Luckey T.D., Reyniers J.A., Gyorgy P., and Forbes M. Germfree animals and liver necrosis. Ann N Y Acad Sci 57 (1954) 932-935
44. Combe E., and Sacquet E. Influence of the axenic state on various nitrogen compounds contained in the caecum of albino rats receiving variable amounts of proteins. C R Acad Sci Hebd Seances Acad Sci D 262 (1966) 685-688
45. Gordon H.A., Wostmann B.S., and Bruckner-Kardoss E. Effects of microbial flora on cardiac output and other elements of blood circulation. Proc Soc Exp Biol Med 114 (1963) 301-304
46. Laroche M.J., Cottart A., Sacquet E., and Charlier H. Absorption of some chemical substances by the gastrointestinal tract of germ-free and conventional rats. Ann Pharm Fr 22 (1964) 333-338
47. Wostmann B.S., Knight P.L., Keeley L.L., and Kan D.F. Metabolism and function of thiamine and naphthoquinones in germfree and conventional rats. Fed Proc 22 (1963) 120-124
48. Danielsson H., and Gustafsson B. On serum-cholesterol levels and neutral fecal sterols in germ-free rats; bile acids and steroids 59. Arch Biochem Biophys 83 (1959) 482-485
49. Gordon H.A. Morphological and physiological characterization of germfree life. Ann N Y Acad Sci 78 (1959) 208-220
50. Reddy B.S., Wostmann B.S., and Pleasants J.R. Iron, copper, and manganese in germfree and conventional rats. J Nutr 86 (1965) 159-168
51. Wostmann B.S., Wiech N.L., and Kung E. Catabolism and elimination of cholesterol in germfree rats. J Lipid Res 7 (1966) 77-82
52. Gordon H.A. Germ-free animals in research: an extension of the pure culture concept. Triangle 7 (1965) 108-121
53. Desplaces A., Zagury D., and Sacquet E. Study of the thyroid function of the germ-free rat. C R Hebd Seances Acad Sci 257 (1963) 756-758
54. Wostmann B.S., Bruckner-Kardoss E., and Knight Jr. P.L. Cecal enlargement, cardiac output, and O2 consumption in germfree rats. Proc Soc Exp Biol Med 128 (1968) 137-141
55. Heneghan J.B. Influence of microbial flora on xylose absorption in rats and mice. Am J Physiol 205 (1963) 417-420
56. Ford D.J., and Coates M.E. Absorption of glucose and vitamins of the B complex by germ-free and conventional chicks. Proc Nutr Soc 30 (1971) 10A-11A
57. Reddy B.S., Pleasants J.R., and Wostmann B.S. Effect of intestinal microflora on calcium, phosphorus and magnesium metabolism in rats. J Nutr 99 (1969) 353-362
58. Baez S., and Gordon H.A. Tone and reactivity of vascular smooth muscle in germfree rat mesentery. J Exp Med 134 (1971) 846-856
59. Loesche W.J. Protein and carbohydrate composition of cecal contents of gnotobiotic rats and mice. Proc Soc Exp Biol Med 128 (1968) 195-199
60. Borgstrom B., Dahlqvist A., Gustafsson B.E., Lundh G., and Malmquist J. Trypsin, invertase and amylase content of feces of germfree rats. Proc Soc Exp Biol Med 102 (1959) 154-155
61. Norin K.E., Gustafsson B.E., and Midtvedt T. Strain differences in faecal tryptic activity of germ-free and conventional rats. Lab Anim 20 (1986) 67-69
62. Strandberg K., Sedvall G., Midtvedt T., and Gustafsson B. Effect of some biologically active amines on the cecum wall of germfree rats. Proc Soc Exp Biol Med 121 (1966) 699-702
63. Dupont J.R., Jervis H.R., and Sprinz H. Auerbach's plexus of the rat cecum in relation to the germfree state. J Comp Neurol 125 (1965) 11-18
64. Abrams G.D., and Bishop J.E. Effect of the normal microbial flora on gastrointestinal motility. Proc Soc Exp Biol Med 126 (1967) 301-304
65. Sacquet E., Garnier H., and Raibaud P. Study of rate of the gastrointestinal transit of spores of a strictly thermophilic strain of Bacillus subtilis in the holoxenic rat, the axenic rat and the cecectomized axenic rat. C R Seances Soc Biol Fil 164 (1970) 532-537
66. Arantes R.M., and Nogueira A.M. Increased intracellular content of enteroglucagon in proximal colon is related to intestinal adaptation to germ-free status. Cell Tissue Res 303 (2001) 447-450
67. Gregor M., Stallmach A., Menge H., and Riecken E.O. The role of gut-glucagon-like immunoreactants in the control of gastrointestinal epithelial cell renewal. Digestion 46 Suppl. 2 (1990) 59-65
68. Yolton D.P., Stanley C., and Savage D.C. Influence of the indigenous gastrointestinal microbial flora on duodenal alkaline phosphatase activity in mice. Infect Immun 3 (1971) 768-773
69. de Both N.J., and Plaisier H. The influence of changing cell kinetics on functional differentiation in the small intestine of the rat. A study of enzymes involved in carbohydrate metabolism. J Histochem Cytochem 22 (1974) 352-360
70. Dai D., Nanthkumar N.N., Newburg D.S., and Walker W.A. Role of oligosaccharides and glycoconjugates in intestinal host defense. J Pediatr Gastroenterol Nutr 30 Suppl. 2 (2000) S23-S33
71. Hooper L.V., Wong M.H., Thelin A., Hansson L., Falk P.G., and Gordon J.I. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291 (2001) 881-884
72. Nanthakumar N.N., Dai D., Meng D., Chaudry N., Newburg D.S., and Walker W.A. Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice. Glycobiology 15 (2005) 221-232
73. Nanthakumar N.N., Dai D., Newburg D.S., and Walker W.A. The role of indigenous microflora in the development of murine intestinal fucosyl- and sialyltransferases. FASEB J 17 (2003) 44-46
74. Lopez-Boado Y.S., Wilson C.L., Hooper L.V., Gordon J.I., Hultgren S.J., and Parks W.C. Bacterial exposure induces and activates matrilysin in mucosal epithelial cells. J Cell Biol 148 (2000) 1305-1315
75. Kozakova H., Stepankova R., Rehakova Z., and Kolinska J. Differences in enterocyte brush border enzyme activities in ageing rats reared in germ-free and conventional conditions. Physiol Res 47 (1998) 253-258
76. Jervis H.R., and Biggers D.C. Mucosal enzymes in the cecum of conventional and germfree mice. Anat Rec 148 (1964) 591-597
77. Dahlqvist A., Bull B., and B.E., and Gustafsson. Rat intestinal 6-bromo-2-naphthyl glycosidase and disaccharidase activities. I. Enzymic properties and distribution in the digestive tract of conventional and germ-free animals. Arch Biochem Biophys 109 (1965) 150-158
78. Bry L., Falk P.G., Midtvedt T., and Gordon J.I. A model of host-microbial interactions in an open mammalian ecosystem. Science 273 (1996) 1380-1383
79. Evrard E., Hoet P.P., Eyssen H., Charlier H., and Sacquet E. Faecal lipids in germ-free and conventional rats. Br J Exp Pathol 45 (1964) 409-414
80. Gustafsson B.E., and Lanke L.S. Bilirubin and urobilins in germfree, ex-germfree, and conventional rats. J Exp Med 112 (1960) 975-981
81. Carlstedt-Duke B., Hoverstad T., Lingaas E., Norin K.E., Saxerholt H., Steinbakk M., et al. Influence of antibiotics on intestinal mucin in healthy subjects. Eur J Clin Microbiol 5 (1986) 634-638
82. Wostmann B.S., and Bruckner-Kardoss E. Oxidation-reduction potentials in cecal contents of germfree and conventional rats. Proc Soc Exp Biol Med 121 (1966) 1111-1114
83. Gustafsson B.E., and Norman A. Urinary calculi in germfree rats. J Exp Med 116 (1962) 273-284
84. Asano T. Modification of cecal size in germfree rats by long-term feeding of anion exchange resin. Am J Physiol 217 (1969) 911-918
85. Asano T. Inorganic ions in cecal content of gnotobiotic rats. Proc Soc Exp Biol Med 124 (1967) 424-430
86. Asano T. Anion concentration in cecal content of germ-free and conventional mice. Proc Soc Exp Biol Med 131 (1969) 1201-1205
87. Quevauviller A., Laroche M.J., Cottart A., Sacquet E., and Charlier E. Anesthetic activity and comparative metabolism of hexobarbital in the germ-free and conventional mouse. Ann Pharm Fr 22 (1964) 339-344
88. Ducluzeau R., Raibaud P., Dickinson A.B., Sacquet E., and Mocquot G. Hydrolysis of urea in vitro and in vivo, in the cecum of gnotobiotic rats, by different bacterial strains isolated from the digestive tract of conventional rats. C R Acad Sci Hebd Seances Acad Sci D 262 (1966) 944-947
89. Hoverstad T., and Midtvedt T. Short-chain fatty acids in germfree mice and rats. J Nutr 116 (1986) 1772-1776
90. Welling G.W., Groen G., Tuinte J.H., Koopman J.P., and Kennis H.M. Biochemical effects on germ-free mice of association with several strains of anaerobic bacteria. J Gen Microbiol 117 (1980) 57-63
91. Lindstedt G., Lindstedt S., and Gustafsson B.E. Mucus in intestinal contents of germfree rats. J Exp Med 121 (1965) 201-213
92. Meslin J.C., Sacquet E., and Guenet J.L. Action of bacterial flora on the morphology and surface mucus of the small intestine of the rat. Ann Biol Anim Biochim Biophys 13 (1973) 203-214
93. Meslin J.C., and Sacquet E. Effects of microflora on the dimensions of enterocyte microvilli in the rat. Reprod Nutr Dev 24 (1984) 307-314
94. Gordon H.A., and Bruckner-Kardoss E. Effect of normal microbial flora on intestinal surface area. Am J Physiol 201 (1961) 175-178
95. Glaister J.R. Factors affecting the lymphoid cells in the small intestinal epithelium of the mouse. Int Arch Allergy Appl Immunol 45 (1973) 719-730
96. Abrams G.D., Bauer H., and Sprinz H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest 12 (1963) 355-364
97. Lesher S., Walburg Jr. H.E., and Sacher Jr. G.A. Generation cycle in the duodenal crypt cells of germ-free and conventional mice. Nature 202 (1964) 884-886
98. Wostmann B., and Bruckner-Kardoss E. Development of cecal distention in germ-free baby rats. Am J Physiol 197 (1959) 1345-1346
99. Pleasants J.R. Characteristics of the germ-free animal. In: Coates M.E. (Ed). The germ free animal in research (1968), Academic Press, London and New York 113-125
100. Hudson J.A., and Luckey T.D. Bacteria induced morphologic changes. Proc Soc Exp Biol Med 116 (1964) 628-631
101. Nuttall G.H.F., and Thierfelder H. Thierisches Leben ohne Baktieren in Verdauungskanal. Hoppe-Seyl. Z. Physiol. Chem. 21 (1895) 109-121
102. Gordon H.A., and Bruckner-Kardoss E. Effect of the normal microbial flora on various tissue elements of the small intestine. Acta Anat (Basel) 44 (1961) 210-225
103. Kenworthy R., and Allen W.D. Influence of diet and bacteria on small intestinal morphology, with special reference to early weaning and Escherichia coli. Studies with germfree and gnotobiotic pigs. J Comp Pathol 76 (1966) 291-296
104. Khoury K.A., Floch M.H., and Hersh T. Small intestinal mucosal cell proliferation and bacterial flora in the conventionalization of the germfree mouse. J Exp Med 130 (1969) 659-670
105. Guenet J.L., Sacquet E., Gueneau G., and Meslin J.C. Action of total microflora of the rat on mitotic activity of Lieberkuhn's crypts. C R Acad Sci Hebd Seances Acad Sci D 270 (1970) 3087-3090
106. Gustafsson B.E., and Maunsbach A.B. Ultrastructure of the enlargec cecum in germfree rats. Z Zellforsch Mikrosk Anat 120 (1971) 555-578
107. He W., Wang M.L., Jiang H.Q., Steppan C.M., Shin M.E., Thurnheer M.C., et al. Bacterial colonization leads to the colonic secretion of RELMbeta/FIZZ2, a novel goblet cell-specific protein. Gastroenterology 125 (2003) 1388-1397
108. Szentkuti L., and Enss M.L. Comparative lectin-histochemistry on the pre-epithelial mucus layer in the distal colon of conventional and germ-free rats. Comp Biochem Physiol A Mol Integr Physiol 119 (1998) 379-386
109. Moreau M.C., Ducluzeau R., Guy-Grand D., and Muller M.C. Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect Immun 21 (1978) 532-539
110. Fahey J.L., and Sell S. The Immunoglobulins of Mice. V. The metabolic (catabolic) properties of five immunoglobulin classes. J Exp Med 122 (1965) 41-58
111. Arnason B.G., Salomon J.C., and Grabar P. Anti-liver antibodies and serum immunoglobulins in the standard and axenic mice; a comparative study after acute hepatic necrosis induced by carbon tetrachlorode (Cc14). C R Hebd Seances Acad Sci 259 (1964) 4882-4885
112. Crabbe P.A., Nash D.R., Bazin H., Eyssen H., and Heremans J.F. Immunohistochemical observations on lymphoid tissues from conventional and germ-free mice. Lab Invest 22 (1970) 448-457
113. Umesaki Y., Setoyama H., Matsumoto S., Imaoka A., and Itoh K. Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun 67 (1999) 3504-3511
114. Helgeland L., Dissen E., Dai K.Z., Midtvedt T., Brandtzaeg P., and Vaage J.T. Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut. Eur J Immunol 34 (2004) 3389-3400
115. Kawaguchi M., Nanno M., Umesaki Y., Matsumoto S., Okada Y., Cai Z., et al. Cytolytic activity of intestinal intraepithelial lymphocytes in germ-free mice is strain dependent and determined by T cells expressing gamma delta T-cell antigen receptors. Proc Natl Acad Sci USA 90 (1993) 8591-8594
116. Imaoka A., Matsumoto S., Setoyama H., Okada Y., and Umesaki Y. Proliferative recruitment of intestinal intraepithelial lymphocytes after microbial colonization of germ-free mice. Eur J Immunol 26 (1996) 945-948
117. Umesaki Y., Setoyama H., Matsumoto S., and Okada Y. Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology 79 (1993) 32-37
118. Mikkelsen H.B., Garbarsch C., Tranum-Jensen J., and Thuneberg L. Macrophages in the small intestinal muscularis externa of embryos, newborn and adult germ-free mice. J Mol Histol 35 (2004) 377-387
119. Umesaki Y., Okada Y., Matsumoto S., Imaoka A., and Setoyama H. Segmented filamentous bacteria are indigenous intestinal bacteria that activate intraepithelial lymphocytes and induce MHC class II molecules and fucosyl asialo GM1 glycolipids on the small intestinal epithelial cells in the ex-germ-free mouse. Microbiol Immunol 39 (1995) 555-562
120. Matsumoto S., Setoyama H., and Umesaki Y. Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization. Gastroenterology 103 (1992) 1777-1782
121. Sobko T., Reinders C., Norin E., Midtvedt T., Gustafsson L.E., and Lundberg J.O. Gastrointestinal nitric oxide generation in germ-free and conventional rats. Am J Physiol Gastrointest Liver Physiol 287 (2004) G993-G997
122. Beaver M.H., and Wostmann B.S. Histamine and 5-hydroxytryptamine in the intestinal tract of germ-free animals, animals harbouring one microbial species and conventional animals. Br J Pharmacol Chemother 19 (1962) 385-393
123. Bos N.A., Meeuwsen C.G., Hooijkaas H., Benner R., Wostmann B.S., and Pleasants J.R. Early development of Ig-secreting cells in young of germ-free BALB/c mice fed a chemically defined ultrafiltered diet. Cell Immunol 105 (1987) 235-245
124. Bos N.A., Meeuwsen C.G., Wostmann B.S., Pleasants J.R., and Benner R. The influence of exogenous antigenic stimulation on the specificity repertoire of background immunoglobulin-secreting cells of different isotypes. Cell Immunol 112 (1988) 371-380
125. Bos N.A., Meeuwsen C.G., Van Wijngaarden P., and Benner R. B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice. II. Analysis of antigen-binding capacities in relation to VH gene usage. Eur J Immunol 19 (1989) 1817-1822
126. Hooijkaas H., Benner R., Pleasants J.R., and Wostmann B.S. Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered "antigen-free" diet. Eur J Immunol 14 (1984) 1127-1130
127. Sprinz H., Kundel D.W., Dammin G.J., Horowitz R.E., Schneider H., and Formal S.B. The response of the germfree guinea pig to oral bacterial challenge with Escherichia coli and Shigella flexneri. Am J Pathol 39 (1961) 681-695
128. Pollard M. The use of germfree animals in virus research. Prog Med Virol 7 (1965) 362-376
129. Bauer H., Horowitz R.E., Levenson S.M., and Popper H. The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am J Pathol 42 (1963) 471-483
130. Olson G.B., and Wostmann B.S. Lymphocytopoiesis, plasmacytopoiesis and cellular proliferation in nonantigenically stimulated germfree mice. J Immunol 97 (1966) 267-274
131. Gustafsson B.E., and Laurell C.B. G Gamma globulins in germ-free rats. J Exp Med 108 (1958) 251-258
132. Wostmann B.S. Recent studies on the serum proteins of germfree animals. Ann N Y Acad Sci 94 (1961) 272-283
133. Thorbecke G.J. Some histological and functional aspects of lymphoid tissue in germfree animals. I. Morphological studies. Ann N Y Acad Sci 78 (1959) 237-246
134. Gustafsson B.E., and Laurell C.B. Gamma globulin production in germfree rats after bacterial contamination. J Exp Med 110 (1959) 675-684
135. Sell S. Immunoglobulins of the Germfree Guinea Pig. J Immunol 93 (1964) 122-131
136. Freitas A.A., Viale A.C., Sundblad A., Heusser C., and Coutinho A. Normal serum immunoglobulins participate in the selection of peripheral B-cell repertoires. Proc Natl Acad Sci USA 88 (1991) 5640-5644
137. Hooijkaas H., van der Linde-Preesman A.A., Bitter W.M., Benner R., Pleasants J.R., and Wostmann B.S. Frequency analysis of functional immunoglobulin C- and V-gene expression by mitogen-reactive B cells in germfree mice fed chemically defined ultra-filtered "antigen-free" diet. J Immunol 134 (1985) 2223-2227
138. Ikari N.S. Bactericidal antibody to Escherichia coli in germ-free mice. Nature 202 (1964) 879-881
139. Wagner M., and Wostmann B.S. Serum protein fractions and antibody studies in gnotobiotic animals reared germfree or monocontaminated. Ann N Y Acad Sci 94 (1961) 210-217
140. Wostmann B.S., and Gordon H.A. Electrophoretic studies on the serum protein pattern of the germfree rat and its changes upon exposure to a conventional bacterial flora. J Immunol 84 (1960) 27-31
141. Ohwaki M., Yasutake N., Yasui H., and Ogura R. A comparative study on the humoral immune responses in germ-free and conventional mice. Immunology 32 (1977) 43-48
142. Horowitz R.E., Bauer H., Paronetto F., Abrams G.D., Watkins K.C., and Popper H. The response of the lymphatic tissue to bacterial antigen. Studies in germfree mice. Am J Pathol 44 (1964) 747-761
143. MacDonald T.T., and Carter P.B. Requirement for a bacterial flora before mice generate cells capable of mediating the delayed hypersensitivity reaction to sheep red blood cells. J Immunol 122 (1979) 2624-2629
144. Wells C., and Balish E. The mitogenic activity of lipopolysaccharide for spleen cells from germfree, conventional, and gnotobiotic rats. Can J Microbiol 25 (1979) 1087-1093
145. Etlinger H.M., and Heusser C.H. T15 dominance in BALB/c mice is not controlled by environmental factors. J Immunol 136 (1986) 1988-1991
146. Lerner E.M. Federation proceedings. Federation of the American societies for experimental biology (1964) 286
147. Walton K.L., Galanko J.A., Sartor R.B., and Fisher N.C. T cell-mediated oral tolerance is intact in germ-free mice. Clin Exp Immunol 143 (2006) 503-512
148. Bos N.A., and Ploplis V.A. Humoral immune response to 2,4-dinitrophenyl--keyhole limpet hemocyanin in antigen-free, germ-free and conventional BALB/c mice. Eur J Immunol 24 (1994) 59-65
149. Salomon J.C. Induction of homologous disease in axenic (germ-free) newborn mice. CR Acad Sci Hebd Seances Acad Sci D 260 (1965) 4862-4864
150. Bauer H., Paronetto F., Burns W.A., and Einheber A. The enhancing effect of the microbial flora on macrophage function and the immune response. A study in germfree mice. J Exp Med 123 (1966) 1013-1024
151. Bakker R., Lasonder E., and Bos N.A. Measurement of affinity in serum samples of antigen-free, germ-free and conventional mice after hyperimmunization with 2,4-dinitrophenyl keyhole limpet hemocyanin, using surface plasmon resonance. Eur J Immunol 25 (1995) 1680-1686
152. Taylor M.J., Rooney J.R., and Blundell G.P. Experimental anthrax in the rat. II. The relative lack of natural resistance in germ-free (Lobund) hosts. Am J Pathol 38 (1961) 625-638
153. Oliveira M.R., Tafuri W.L., Afonso L.C., Oliveira M.A., Nicoli J.R., Vieira E.C., et al. Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions. Parasitology 131 (2005) 477-488
154. Inagaki H., Suzuki T., Nomoto K., and Yoshikai Y. Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation. Infect Immun 64 (1996) 3280-3287
155. Martin L.K., Einheber A., Porro R.F., Sadun E.H., and Bauer H. Plasmodium berghei infections in gnotobiotic mice and rats: parasitologic, immunologic and histopathologic observations. Mil Med 131 Suppl. (1966) 870-889
156. Finerty J.F., Evans C.B., and Hyde C.L. Plasmodium berghei and Eperythrozoon coccoides: antibody and immunoglobulin synthesis in germfree and conventional mice simultaneously infected. Exp Parasitol 34 (1973) 76-84
157. Schaffer J., Beamer P.R., Trexler P.C., Breidenbach G., and Walcher D.N. Response of germ-free animals to experimental virus monocontamination. I. Observation on Coxsackie B virus. Proc Soc Exp Biol Med 112 (1963) 561-564
158. Dolowy W.C., and Muldoon R.L. Studies of germfree animals. I. Response of mice to infection with influenza a virus. Proc Soc Exp Biol Med 116 (1964) 365-371
159. Bhatt P.N., Jacoby R.O., and Jonas A.M. Respiratory infection in mice with sialodacryoadenitis virus, a coronavirus of rats. Infect Immun 18 (1977) 823-827
160. Tennant R.W., Parker J.C., and Ward T.G. Virus studies with germfree mice. Ii. Comparative responses of germfree mice to virus infection. J Natl Cancer Inst 34 (1965) 381-387
161. Giannini M.S. The specific anti-parasite immune responses of germ-free and conventional rats infected with Trypanosoma lewisi. J Parasitol 73 (1987) 144-148
162. Balish E., and Filutowicz H. Serum antibody response of gnotobiotic athymic and euthymic mice following alimentary tract colonization and infection with Candida albicans. Can J Microbiol 37 (1991) 204-210
163. De Somer P., and Billiau A. Interferon production by the spleen of rats after intravenous injection of Sindbis virus or heat-killed Escherichia coli. Arch Gesamte Virusforsch 19 (1966) 143-154