Helicobactor pylori pp 15-29 | Cite as
Helicobacter hepaticus and Helicobacter bilis: proinflammatory modulators of enterohepatic disease
Abstract
Using Steiner’s silver stain a bacterium with spiral to curved morphology was observed in livers of control A/JCr mice with hepatitis, hepatic adenomas and hepatocellular carcinomas1. A Gram-negative bacterium with bipolar, single-sheathed flagella, isolated from these mice with diseased livers, maintained on a long-term carcinogenicity study, was characterized and named H. hepaticus 2. Since its original observation in A/JCr mice in 1991, H. hepaticus is now known to be prevalent in many mouse colonies, commercial and academic, throughout the world3. In addition to A/JCr mice, H. hepaticus causes hepatitis in BALB/cCr, SJL/NCr, SCID/NCr, C3H/ HeNCr mice and AxB recombinant strains. Like AJ/CR mice, H. hepaticus infection in B6C3F1 and AxB mice is associated with liver cancer. Because H. hepaticus’ ecological niche is the lower bowel, and the organism can also be readily isolated from the faeces, faecal-oral transmission is suspected. For example, H. hepaticus was isolated from either the caecum or the colon of 100% of A/JCr mice surveyed during a longitudinal study4. Thus, for routine diagnosis of H. hepaticus infection in infected mice, isolation should be attempted from the distal part of the intestine, not the liver parenchyma. The persistent nature of the infection, usually without overt clinical signs in wild-type mice, may in part contribute to the high prevalence of H. hepaticus in commercial and academic mouse colonies3,5. Recently, because of the negative impact of Helicobacter infections on biomedical research, considerable effort has been expended to derive Helicobacter-free colonies at several commercial vendors in the United States.
Keywords
Scid Mouse Rectal Prolapse Recombination Activate Gene Cytolethal Distend Toxin Lower BowelPreview
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References
- 1.Ward JM, Fox JG, Anver MR et al. Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. J Nat Cancer Inst. 1994; 86: 1222–7.PubMedCrossRefGoogle Scholar
- 2.Fox JG, Dewhirst FE, Tully JG et al. Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice. J Clin Microbiol. 1994; 32: 1238–45.PubMedGoogle Scholar
- 3.Shames B, Fox JG, Dewhirst FE, Yan L, Shen Z, Taylor NS. Identification of widespread Helicobacter hepaticus infection in feces in commercial mouse colonies by culture and PCR assay. J Clin Microbiol. 1995; 33: 2968–72.PubMedGoogle Scholar
- 4.Fox JG, Li X, Yan L et al. Chronic proliferative hepatitis in A/JCr mice associated with persistent Helicobacter hepaticus infection: a model of Helicobacter-induced carcinogenesis. Infect Immun. 1996; 64: 1548–58.PubMedGoogle Scholar
- 5.Foltz C, Fox JG, Yan L, Shames B. Evaluation of antibiotic therapies for the eradication of Helicobacter hepaticus. Antimicrob Agents Chemother. 1995; 36: 1292–4.CrossRefGoogle Scholar
- 6.Ward JM, Anver MR, Haines DC, Benveniste RE. Chronic active hepatitis in mice caused by Helicobacter hepaticus. Am J Pathol. 1994; 145: 959–68.PubMedGoogle Scholar
- 7.Sundberg JP, Fox JG, Ward JM, Bedigian HG. Idiopathic focal hepatic necrosis in inbred laboratory mice. In: Jones TC, Popp JA, Mohr V, editors. Digestive System, 2nd edn. New York: Springer-Verlag, 1997: 213–17.CrossRefGoogle Scholar
- 8.Ihrig M, Schrenze M, Fox JG. Differential susceptibility to hepatic inflammation and proliferation in AXB recombinant inbred mice chronically infected with Helicobacter hepaticus. Am J Pathol. 1999; 155: 571–82.PubMedCrossRefGoogle Scholar
- 9.Fox JG, Yan L, Shames B, Campbell J, Murphy JC, Li X. Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus. Infect Immun. 1996; 64: 3673–81.PubMedGoogle Scholar
- 10.Ward JM, Bevenist RE, Fox CH, Battles JK, Gonda MA, Tully JG. Autoimmunity in chronic active Helicobacter hepaticus of mice: serum antibodies and expression of heat shock protein 70 in liver. Am J Pathol. 1996; 148: 509–17.PubMedGoogle Scholar
- 11.Whary MT, Morgan TJ, Dangler CA, Gaudes KJ, Taylor NS. Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Thl cell-mediated immune response. Infect Immun. 1998; 66: 3142–48.PubMedGoogle Scholar
- 12.Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Buschenfelde KHMZ. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol. 1995; 102: 448–55.PubMedCrossRefGoogle Scholar
- 13.Berg DJ, Davidson N, Kuhn R et al. Enterocolitis and colon cancer in interleukin 10 deficient mice are associated with averrant cytokine production and CD4. + Thl-like response. J Clin Invest. 1996; 98: 1010–20.PubMedCrossRefGoogle Scholar
- 14.Kullberg MC, Ward JM, Gorelick PL et al. Helicobacter hepaticus triggers colitis in specific pathogen free interleukin-l0 (IL-10) deficient mice through an IL-12 and gamma interferon-dependent mechanism. Infect Immun. 1998; 66: 5157–66.PubMedGoogle Scholar
- 15.Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-l0-deficient mice develop chronic enterocolitis. Cell. 1993; 75: 263–74.PubMedCrossRefGoogle Scholar
- 16.Seibold F, Brandwein S, Simpson S, Terhorst C, Elson CO. pANCA represents a cross-reactivity to enteric bacterial antigens. J Clin Immunol. 1998; 18: 153–60.PubMedCrossRefGoogle Scholar
- 17.Abo T, Ohteki T, Seki S et al. The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria. J Exp Med. 1991; 174: 417–24.PubMedCrossRefGoogle Scholar
- 18.Nyska A, Maronpot R, Eldridge S, Haseman J, Hailey J. Alteration in cell kinetics in control B6C3F1 mice infected with Helicobacter hepaticus. Toxicol Pathol. 1997; 25: 591–6.PubMedCrossRefGoogle Scholar
- 19.Sipowicz MA, Chomarat P, Diwan BA et al. Increase oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected with Helicohacter hepaticus. Am J Pathol. 1997; 151: 933–41.PubMedGoogle Scholar
- 20.Luperchio S, Tamir S, Tannenbaum SR. NO-induced oxidative stress and glutathione metabolism in rodent and human cells. Free Rad Biol Med. 1996; 21: 513–19.PubMedCrossRefGoogle Scholar
- 21.Singh R, Leuratti C, Josyula S et al. Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus. Carcinogenesis. 2001; 22: 1281–7.PubMedCrossRefGoogle Scholar
- 22.Diwan BA, Rice JM, Oshima M, Ward JM. Interstain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV and DBA/2NCr mice. Carcinogenesis. 1986; 7: 215–20.PubMedCrossRefGoogle Scholar
- 23.Weghorst CM, Pereira MA, Klaunig JE. Strain differences in hepatic tumor promotion by phenobarbital in diethylnitrosamine-and dimethylnitrosamine-initiated infant male mice. Carcinogenesis. 1989; 10: 1409–12.PubMedCrossRefGoogle Scholar
- 24.Canella KA, Diwan BA, Gorelick PL et al. Liver tumorigenesis by Helicobacter hepaticus: considerations of mechanism. In Vivo. 1996; 10: 285–92.PubMedGoogle Scholar
- 25.Diwan BA, Ward JM, Ramljak D, Anderson LM. Promotion by Helicobacter hepaticusinduced hepatitis of hepatic tumors initiated by N-nitrosodimenthylamine in maleA/JCr mice. Toxicol Pathol. 1997; 25: 597–605.PubMedCrossRefGoogle Scholar
- 26.Sipowicz MA, Weghorst CM, Shiao YH et al. Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice. Carcinogenesis. 1997; 18: 233–6.PubMedCrossRefGoogle Scholar
- 27.Fox JG, Yan LL, Dewhirst FE et al. Helicobacter bilis sp. nov., a novel Helicobacter isolated from bile, livers, and intestines of aged, inbred mice. J Clin Microbiol. 1995; 33: 445–54.PubMedGoogle Scholar
- 28.Foster JR. Bacterial infection of the common bile duct in chronic fascioliasis in the rat. J Comp Pathol. 1984; 94: 175–81.PubMedCrossRefGoogle Scholar
- 29.Fox JG. The non-H. pylori helicobacters: their expanding role in gastrointestinal and systemic diseases. Gut. 2002; 50: 273–83.PubMedCrossRefGoogle Scholar
- 30.Fox JG, Dewhirst FE, Shen Z et al. Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis. Gastroenterology. 1998; 114: 755–63.PubMedCrossRefGoogle Scholar
- 31.Matsukura N, Yokomuro S, Yamada S et al. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res. 2002; 93: 842–7.PubMedCrossRefGoogle Scholar
- 32.Ge Z, Doig P, Fox JG. Characterization of proteins in the outer membrane preparation of a murine pathogen, Helicobacter bilis. Infect Immun. 2001; 69: 3502–6.PubMedCrossRefGoogle Scholar
- 33.Kornilovs’ka I, Nilsson I, Utt M, Ljungh A, Wadstrom T. Immunogenic proteins of Helicobacter pullorum, Hellicobacter bilis and Helicobacter hepaticus identified by two-dimensional gel electrophoresis and immunoblotting. Proteomics. 2002; 2: 775–83.PubMedCrossRefGoogle Scholar
- 34.Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell. 1993; 75: 274–82.PubMedCrossRefGoogle Scholar
- 35.Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993; 75: 253–61.PubMedCrossRefGoogle Scholar
- 36.Baribault H, Penner L, Lozzo RV, Wilson-Heiner M. Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev. 1994; 8: 2964–73.PubMedCrossRefGoogle Scholar
- 37.Hermiston ML, Gordon JI. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 1995; 270: 1203–7.PubMedCrossRefGoogle Scholar
- 38.Mashimo H, Wu DC, Podolsky DK, Fishman MC. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science. 1996; 274: 262–5.PubMedCrossRefGoogle Scholar
- 39.Foltz CJ, Morgan TJ, Dangler CA, Fox JG. Inflammatory bowel disease spontaneously arising in multidrug resistant gene knockout (mdr la) mice. Vet Pathol. 1997; 34: 509.Google Scholar
- 40.Maggio-Price L, Shows D, Waggie K et al. Helicobacter bilis infection accelerates and H. hepaticus infection delays the development of colitis in multiple drug resistance-deficient (mdrla-/-) mice. Am J Pathol. 2002; 160: 739–51.PubMedCrossRefGoogle Scholar
- 41.Panwala CM, Jones JC, Viney JL. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdrla, spontaneously develop colitis. J Immunol. 1998; 161: 5733–44.PubMedGoogle Scholar
- 42.Erdman S, Poutahidis T, Rogers A et al. CD4+ CD45Rblo regulatory T lymphocytes inhibit microbially-induced colon cancer in Rag2-deficient mice. Am J Pathol. 2003; 162: 691–702.PubMedCrossRefGoogle Scholar
- 43.Poutahidis T, Erdman S, Horwitz B, Rogers A, Fox J. Susceptibility of three different immunodeficient mouse strains in Helicobacter hepaticus-induced typhlocolitis and lower bowel cancer. Gut. 2002; 51: A53.Google Scholar
- 44.Ma A, Datta M, Margosian E, Chen J, Horak I. T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice. J Exp Med. 1995; 182: 1567–72.PubMedCrossRefGoogle Scholar
- 45.Sadlack B, Lohler J, Schorle H et al. Generalized autoimmune disease in interleukin2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4 * T cells. Eur J Immunol. 1995; 25: 3053–9.PubMedCrossRefGoogle Scholar
- 46.Powrie F, Leach M, Mauze S, Caddie L, Coffman R. Phenotypically distinct subsets of CD4+ T cells induce or protect from intestinal inflammation in C.B-17 scid mice. Int Immunol. 1993; 5: 1461–71.PubMedCrossRefGoogle Scholar
- 47.Powrie F, Leach M, Mauze S, Menon S, Caddle L, Coffman R. Inhibition of Thl response prevents inflammatory bowel disease in scid mice reconstituted with CD45RB hi CD4+ T cells. Immunity. 1994; 1: 553–62.PubMedCrossRefGoogle Scholar
- 48.Kullberg MC, Rothfuchs AG, Jankovic D et al. Helicobacter hepaticus-induced colitis in interleukin-l0-deficient mice: cytokine requirements for the induction and maintenance of intestinal inflammation. Infect Immun. 2001; 69: 4232–41.PubMedCrossRefGoogle Scholar
- 49.von Freeden-Jeffry U, Davidson N, Wiler R, Fort M, Burdach S, Murray R. IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis. J Immunol. 1998; 15: 5673–80.Google Scholar
- 50.Dianda L, Hanby AM, Wright NA, Sebesteny A, Hayday AC, Owen M. T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. Am J Pathol. 1997; 150: 91–7.PubMedGoogle Scholar
- 51.Fox JG, Gorelick PL, Kullberg MC, Ge Z, Dewhirst FE, Ward JM. A novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice. Infect Immun. 1999; 67: 1757–62.PubMedGoogle Scholar
- 52.Fox JG, MacGregor J, Shen Z, Li X, Lewis R, Dangler CA. Comparison of methods to identify Helicobacter hepaticus in B6C3F, used in a carcinogenesis bioassay. J Clin Microbiol. 1998; 36: 1382–7.PubMedGoogle Scholar
- 53.Franklin CL, Gorelick PL, Riley LK et al. Helicobacter typhlonius sp. nov., a novel murine urease-negative Helicobacter species. J Clin Microbiol. 2001; 39: 3920–6.PubMedCrossRefGoogle Scholar
- 54.Li X, Fox JG, Whary MT, Yan L, Shames B, Zhao Z. Scid/NCr mice naturally infected with Helicobacter hepaticus develop progressive hepatitis, proliferative typhlitis and colitis. Infect Immun. 1998; 66: 5477–84.PubMedGoogle Scholar
- 55.Ward JM, Anver MR, Haines DC et al. Inflammatory large bowel disease in immunodeficient mice naturally infected with Helicobacter hepaticus. Lab Anim Sci. 1996; 46: 1–20.Google Scholar
- 56.Foltz CJ, Fox JG, Cahill RJ et al. Spontaneous inflammatory bowel disease in multiple mutant mouse lines: association with colonization by Helicobacter hepaticus. Helicobacter. 1998; 3: 69–78.PubMedCrossRefGoogle Scholar
- 57.Erdman S, Fox JG, Dangler CA, Feldman D, Horwitz BH. Typhlocolitis in NF-kappa B-deficient mice. J Immunol. 2001; 166: 1443–7.PubMedGoogle Scholar
- 58.Shomer NH, Dangler CA, Marini R, Fox JG. Helicobacter bilis/Helicobacter rodentium co-infection associated with diarrhea in a colony of scid mice. Lab Anim Sci. 1998; 48: 455–9.PubMedGoogle Scholar
- 59.Cahill RJ, Foltz CJ, Fox JG, Danguer CA, Powrie F, Schauer DB. Inflammatory bowel disease: an immune mediated condition triggered by bacterial infection with Helicobacter hepaticus. Infect Immun. 1997; 65: 3126–31.PubMedGoogle Scholar
- 60.Shomer NH, Dangler CA, Schrenzel MD, Fox JG. Helicobacter bilis induced inflammatory bowel desease (IBD) in defined flora scid mice. Infect Immun. 1997; 65: 4858–64.PubMedGoogle Scholar
- 61.Haines DC, Gorlick PL, Battles JK et al. Natural and experimental inflammatory large bowel disease in immunodeficient rats infected with Helicobacter bilis. Vet Pathol. 1998; 35: 202–8.PubMedCrossRefGoogle Scholar
- 62.Chin EY, Dangler CA, Fox JG, Schauer DB. Helicobacter hepaticus infection triggers inflammatory bowel disease in T cell receptor alpha beta deficient mice. Comp Med. 2000; 50: 586–92.PubMedGoogle Scholar
- 63.Kullberg MC, Jankovic D, Gorelick PL et al. Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. J Exp Med. 2002; 196: 505–15.PubMedCrossRefGoogle Scholar
- 64.Suerbaum S, Josenhans C, Sterzenbach T et al. The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus. (Submitted). Google Scholar
- 65.Suerbaum S, Josenhans C, Frosch M et al. Determining the whole genome sequence of Helicobacter hepaticus ATCC 51449. Int J Med Microbiol. 2001; 291: M17.Google Scholar
- 66.Young VB, Knox KA and Schauer DB. Cytolethal distending toxin sequence and activity in the enterohepatic pathogen Helicobacter hepaticus. Infect Immun. 2000; 68: 184–91.PubMedCrossRefGoogle Scholar
- 67.Taylor NS, Fox JG, Yan L. In-vitro hepatotoxic factor in Helicobacter hepaticus, H. pylori and Helicobacter species. J Med Microbiol. 1995; 42: 48–52.PubMedCrossRefGoogle Scholar
- 68.Beckwith CS, McGee DJ, Mobley HL, Riley LK. Cloning, expression, and catalytic activity of Helicobacter hepaticus urease. Infect Immun. 2001; 69: 5914–20.PubMedCrossRefGoogle Scholar
- 69.Akada JK, Shirai M, Takeuchi H, Tsuda M, Nakazawa T. Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH. Mol Microbiol. 2000; 36: 1071–84.PubMedCrossRefGoogle Scholar
- 70.Labigne A, Cussac V, Courcoux P. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol. 1992; 173: 1920–31.Google Scholar
- 71.Scott DR, Marcus EA, Weeks DL, Lee A, Melchers K, Sachs G. Expression of the Helicobacter pylori urel gene is required for acidic pH activation of cytoplasmic urease. Infect Immun 2000; 68: 470–7.PubMedCrossRefGoogle Scholar
- 72.Weeks DL, Eskandari S, Scott DR, Sachs G. A H + -gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science. 2000; 287: 482–5.PubMedCrossRefGoogle Scholar
- 73.Skouloubris S, Thiberge JM, Labigne A, De Reuse H. The Helicobacter pylori Ure! protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect Immun. 1998; 66: 4517–21.PubMedGoogle Scholar
- 74.Monteiro MA, Zheng PY, Appelmelk BJ, Perry MB. The lipopolysaccharide in Helicobacter mustelae type strain ATCC 43772 expresses the monofucosyl A type 1 histo-blood group epitope. FEMS Microbiol Lett. 1997; 154: 103–9.PubMedCrossRefGoogle Scholar
- 75.Moran AP. Helicohacter pylori lipopolysaccharide-mediated gastric and extragastric pathology. J Physiol Pharmacol. 1999; 50: 787–805.PubMedGoogle Scholar
- 76.Hynes SO, Ferris JA, Fox JG et al.Serological and chemical characterization of lipopolysaccharides from gastric and enterohepatic helicobacters. (Submitted).Google Scholar
- 77.Karlsson KA. The human gastric colonizer Helicobacter pylori: a challenge for host-parasite glycobiology. Glycobiology. 2000; 10: 761–71.PubMedCrossRefGoogle Scholar