Helicobacter induced hepatitis and tumorigenesis

Summary

Principal Investigator: James Fox
Affiliation: Massachusetts Institute of Technology
Country: USA
Abstract: Since our isolation and naming of H. hepaticus and elucidating it causes hepatitis and hepatocellular carcinoma in A/J, AGAFx, B6C3F1 and AXB mice, several additional novel helicobacters have been identified in hepatobiliary tissue of both humans and animals. To continue dissecting the pathogenesis of these novel enterohepatic helicobacters, we have recently completed sequencing the genome of the prototype of these emerging enterohepatic pathogens, H. hepaticus. Using this invaluable sequence data, we can study in detail, with the use of isogenic mutants how different virulence genes play a role in chronic inflammation and tumor induction. Furthermore, given H. hepaticus recognized tumor promoting ability with hepatocarcinogens and the increasing recognition of helicobacters in diseased liver tissue of humans where hepatitis B and C virus in infection is endemic, we want to ascertain whether H. hepaticus can synergize with viral proteins to induced hepatocellular carcinomas. Finally, given the ecological niche of these helicobacters in liver is the bile canaliculi, we will explore how helicobacter products or putative virulence genes of H. hepaticus affect colonization dynamics and physiological properties of bile in vivo. Helicobacter hepaticus induced hepatitis and hepatocellular carcinoma in laboratory mice provides a powerful model system for the study of human liver disease and liver cancer. Like the human conditions, disease in the mouse model is multifactorial, with genetic and environmental factors contributing to pathogenesis. The complexity of the system necessitates parallel investigation into bacterial virulence factors, gene expression changes in liver tissue, adaptive immune changes driven by cytokines, biochemical changes in bile and acute phase response components in plasma, and of course lesion development in the liver. This proposal takes advantage of cutting-edge technology to investigate each aspect of disease pathogenesis in this model. A long-term goal is to integrate information gained in each of these areas to build a complete picture of the molecular and cellular mechanisms involved in hepatitis and hepatocellular carcinoma. In this way, our focus will shift over the next 5 years from individual Specific Aims to synergistic areas of overlap between candidate bacterial virulence factors, bacterial expression profile analysis, host expression profile analysis (at the cell, tissue, and organ level), and proteome analysis (using immunohistochemistry, western analysis, and analytic biochemistry). A more complete understanding of the etiopathogenesis of hepatobiliary disease and hepatocellular carcinoma is likely to result in new strategies for treatment and prevention of these important human diseases.
Funding Period: 1995-05-01 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens
    J G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Gut 59:88-97. 2010
  2. doi Helicobacter hepaticus urease is not required for intestinal colonization but promotes hepatic inflammation in male A/JCr mice
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Microb Pathog 45:18-24. 2008
  3. pmc Helicobacter hepaticus infection promotes colon tumorigenesis in the BALB/c-Rag2(-/-) Apc(Min/+) mouse
    Claude M Nagamine
    Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Infect Immun 76:2758-66. 2008
  4. pmc Genetic susceptibility to chronic hepatitis is inherited codominantly in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice, and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune function-a
    Alexis Garcia
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave 16 825, Cambridge, MA 02139, USA
    Infect Immun 76:1866-76. 2008
  5. ncbi Hepatocellular carcinoma associated with liver-gender disruption in male mice
    Arlin B Rogers
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 67:11536-46. 2007
  6. pmc Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice
    James G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Am J Pathol 171:1520-8. 2007
  7. pmc Isolation and characterization of a novel helicobacter species, "Helicobacter macacae," from rhesus monkeys with and without chronic idiopathic colitis
    James G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Clin Microbiol 45:4061-3. 2007
  8. pmc T-cell function is critical for murine cholesterol gallstone formation
    Kirk J Maurer
    Department of Biological Engineering, Massachusetts Institute of Technology, Boston, Massachusetts, USA
    Gastroenterology 133:1304-15. 2007
  9. ncbi Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma
    Theofilos Poutahidis
    Division of Comparative Medicine
    Carcinogenesis 28:2614-23. 2007
  10. pmc c-Rel is essential for the development of innate and T cell-induced colitis
    Yanyan Wang
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 180:8118-25. 2008

Scientific Experts

  • Z Ge
  • James Fox
  • SUSAN ERDMAN
  • KIRK JAMES MAURER
  • M T Whary
  • Alexis Garcia
  • Paola Pisani
  • Arlin B Rogers
  • Varada P Rao
  • Theofilos Poutahidis
  • Bruce H Horwitz
  • Torsten Sterzenbach
  • Prashant R Nambiar
  • David B Schauer
  • Sebastian Suerbaum
  • Floyd E Dewhirst
  • Jeremy A Pena
  • Zeli Shen
  • Barry H Rickman
  • Koichiro Watanabe
  • Yan Feng
  • Shilu Xu
  • Christine Josenhans
  • Nancy S Taylor
  • Z Shen
  • Laura B Lemke
  • Elizabeth J Theve
  • Yanyan Wang
  • Claude M Nagamine
  • Birgit Brenneke
  • Essam J Alyamani
  • Anne Davidson
  • James Versalovic
  • Yan Yan Wang
  • Michal F Tomczak
  • Robin Crisler-Roberts
  • Bruce J Paster
  • Ingrid L Bergin
  • Samuel R Boutin
  • S Xu
  • Sureshkumar Muthupalani
  • B Rickman
  • Y Feng
  • S R Boutin
  • K M Clapp
  • Jessika Schulze
  • David R Bell
  • Masahiro Ohtani
  • Wiebke Behrens
  • Jane J Sohn
  • Lucie Bartonickova
  • Elena Katzowitsch
  • Elaine Y Chin
  • Erin A Jackson
  • Katherine Schlieper
  • Toshio Fujioka
  • Koli Taghizadeh
  • Friederike Kops
  • Kathleen S Cormier
  • Angela M Major
  • Franz von Goetz
  • Kevin M Haigis
  • Christie L Taylor
  • Sae Kyung Lee
  • Petra Brandt
  • Prashant Nambiar
  • Barry Rickman
  • Chakib Boussahmain
  • David Luchetti
  • Lauren N Stokes
  • Kem B Singletary
  • Tsute Chen
  • Michael S Scimeca
  • Tahani Boumenna
  • Vivian Ng
  • Mark Kidd
  • Michael T Kearney
  • Irvin M Modlin
  • Christopher S Roberts
  • Sandra Y Li
  • David G Baker
  • Sandy Xu

Detail Information

Publications43

  1. pmc Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens
    J G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Gut 59:88-97. 2010
    ..Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models...
  2. doi Helicobacter hepaticus urease is not required for intestinal colonization but promotes hepatic inflammation in male A/JCr mice
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Microb Pathog 45:18-24. 2008
    ..These results indicate that H. hepaticus urease activity plays a crucial role in hepatic disease but is not required for cecal colonization by H. hepaticus...
  3. pmc Helicobacter hepaticus infection promotes colon tumorigenesis in the BALB/c-Rag2(-/-) Apc(Min/+) mouse
    Claude M Nagamine
    Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Infect Immun 76:2758-66. 2008
    ..5% versus 1.7%, respectively). The data suggest that H. hepaticus, which is present in many research colonies, promotes colon tumorigenesis in the BALB-RagMin mouse and that it has the potential to confound colon tumorigenesis studies...
  4. pmc Genetic susceptibility to chronic hepatitis is inherited codominantly in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice, and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune function-a
    Alexis Garcia
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave 16 825, Cambridge, MA 02139, USA
    Infect Immun 76:1866-76. 2008
    ..The use of AB6F1 and B6AF1 mice, as well as genetically engineered mice, on a C57BL/6 background will allow studies investigating the role of chronic microbial hepatitis and steatohepatitis in the pathogenesis of liver cancer...
  5. ncbi Hepatocellular carcinoma associated with liver-gender disruption in male mice
    Arlin B Rogers
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 67:11536-46. 2007
    ..This model introduces a novel mechanism of inflammation-associated carcinogenesis consistent with male-predominant HCC risk...
  6. pmc Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice
    James G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Am J Pathol 171:1520-8. 2007
    ..pylori-infected mice at 19 months pi. These data support a protective role for TFF2 in part by modulating levels of gastric interferon-gamma in the development of H. pylori-associated premalignancy of the distal stomach...
  7. pmc Isolation and characterization of a novel helicobacter species, "Helicobacter macacae," from rhesus monkeys with and without chronic idiopathic colitis
    James G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Clin Microbiol 45:4061-3. 2007
    ..All eight strains of H. macacae had 99.5% identical 16S rRNA sequences...
  8. pmc T-cell function is critical for murine cholesterol gallstone formation
    Kirk J Maurer
    Department of Biological Engineering, Massachusetts Institute of Technology, Boston, Massachusetts, USA
    Gastroenterology 133:1304-15. 2007
    ..Although gallbladder inflammation is believed to be common during cholelithogenesis, the role of immunologic factors is unknown...
  9. ncbi Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma
    Theofilos Poutahidis
    Division of Comparative Medicine
    Carcinogenesis 28:2614-23. 2007
    ..These data provide insights into etiopathogenesis of inflammation-associated epithelial invasion and maintenance of epithelial homeostasis...
  10. pmc c-Rel is essential for the development of innate and T cell-induced colitis
    Yanyan Wang
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 180:8118-25. 2008
    ..Thus, c-Rel plays a critical role in regulating the innate inflammatory response to microflora within the lower bowel, likely through its ability to modulate expression of IL-12/23 family members...
  11. pmc Helicobacter hepaticus HHGI1 is a pathogenicity island associated with typhlocolitis in B6.129-IL10 tm1Cgn mice
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Microbes Infect 10:726-33. 2008
    ..05) at 13 WPI. These results demonstrate that genes in the HHGI1 contribute to the pathogenicity of H. hepaticus, at least in part via up-regulation of proinflammatory mediators IFN-gamma, TNF-alpha and IL-17a...
  12. pmc Sex hormone influence on hepatitis in young male A/JCr mice infected with Helicobacter hepaticus
    Elizabeth J Theve
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Infect Immun 76:4071-8. 2008
    ..hepaticus-induced hepatitis in young male mice, whereas androgen receptor agonism does not worsen disease. This raises the possibility of targeted hormonal therapy in young male patients with childhood-acquired HBV...
  13. pmc Chronic hepatitis, hepatic dysplasia, fibrosis, and biliary hyperplasia in hamsters naturally infected with a novel Helicobacter classified in the H. bilis cluster
    J G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave, Bldg 16 825, Cambridge, MA 02139, USA
    J Clin Microbiol 47:3673-81. 2009
    ..bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans...
  14. pmc Cytolethal distending toxin promotes Helicobacter cinaedi-associated typhlocolitis in interleukin-10-deficient mice
    Z Shen
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Infect Immun 77:2508-16. 2009
    ..These results indicate that WT(Hc) can be used to model inflammatory bowel disease in IL-10(-/-) mice and that CDT contributes to the virulence of H. cinaedi...
  15. pmc Concurrent Helicobacter bilis infection in C57BL/6 mice attenuates proinflammatory H. pylori-induced gastric pathology
    Laura B Lemke
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave, Bldg 16 825, Cambridge, MA 02139, USA
    Infect Immun 77:2147-58. 2009
    ..pylori infection, particularly in developing countries, may occur where coinfection with lower bowel helicobacters and H. pylori may be common...
  16. pmc Nitric oxide and TNF-alpha trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice
    S E Erdman
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 106:1027-32. 2009
    ..Collectively, these results confirm essential roles for inflammation, increased TNF-alpha expression, and elevated NO production in colon carcinogenesis...
  17. pmc Roles of infection, inflammation, and the immune system in cholesterol gallstone formation
    Kirk J Maurer
    Division of Gastroenterology, Brigham and Women s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 136:425-40. 2009
    ....
  18. pmc Cytotoxic-T-lymphocyte-associated antigen 4 blockade abrogates protection by regulatory T cells in a mouse model of microbially induced innate immune-driven colitis
    Koichiro Watanabe
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA
    Infect Immun 76:5834-42. 2008
    ....
  19. pmc Role of the Helicobacter hepaticus flagellar sigma factor FliA in gene regulation and murine colonization
    Torsten Sterzenbach
    Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    J Bacteriol 190:6398-408. 2008
    ..flaA_1 mutants which had flagella but displayed reduced motility did not colonize mice, indicating that motility is required for intestinal colonization by H. hepaticus and that the presence of flagella alone is not sufficient...
  20. pmc Cross-reactivity between immune responses to Helicobacter bilis and Helicobacter pylori in a population in Thailand at high risk of developing cholangiocarcinoma
    Paola Pisani
    Descriptive Epidemiology Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 03, France
    Clin Vaccine Immunol 15:1363-8. 2008
    ..We found high cross-reactivity between the immune responses to H. pylori and H. bilis antigens. More-specific H. bilis antigens need to be isolated to develop serologic tests suitable for epidemiological studies...
  21. pmc Enterohepatic Helicobacter species are prevalent in mice from commercial and academic institutions in Asia, Europe, and North America
    Nancy S Taylor
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg 16, Rm 825C, Cambridge, MA 02139, USA
    J Clin Microbiol 45:2166-72. 2007
    ..These results indicate that a broad range of Helicobacter spp. infect mouse research colonies. The potential impact of these organisms on in vivo experiments continues to be an important issue for mice being used for biomedical research...
  22. ncbi Bacterial cytolethal distending toxin promotes the development of dysplasia in a model of microbially induced hepatocarcinogenesis
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cell Microbiol 9:2070-80. 2007
    ....
  23. ncbi Helicobacter hepaticus catalase shares surface-predicted epitopes with mammalian catalases
    Essam J Alyamani
    Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 01225, USA
    Microbiology 153:1006-16. 2007
    ..hepaticus catalase. Catalases are highly conserved enzymes in bacteria and mammals that may contribute to autoimmune responses in animals infected with catalase-producing pathogens...
  24. ncbi Proinflammatory CD4+ CD45RB(hi) lymphocytes promote mammary and intestinal carcinogenesis in Apc(Min/+) mice
    Varada P Rao
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 66:57-61. 2006
    ..These findings define a novel mouse model of inflammation-driven mammary carcinoma and suggest that epithelial carcinogenesis can be mitigated by anti-inflammatory cells and cytokines known to regulate IBD in humans and mice...
  25. pmc Different Helicobacter hepaticus strains with variable genomic content induce various degrees of hepatitis
    Samuel R Boutin
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16 825C, Cambridge, MA 02139, USA
    Infect Immun 73:8449-52. 2005
    ..Mice infected with HhG and HhNET developed less-severe hepatitis than male A/JCr mice infected with Hh3B1...
  26. pmc Discordant 16S and 23S rRNA gene phylogenies for the genus Helicobacter: implications for phylogenetic inference and systematics
    Floyd E Dewhirst
    Department of Molecular Genetics, The Forsyth Institute, Boston, Massachusetts 02115, USA
    J Bacteriol 187:6106-18. 2005
    ..IVSs were found in helices 10, 25, and 45, as well as between helices 31' and 27'. Simultaneous insertion of IVSs at three sites was found in H. mesocricetorum...
  27. ncbi Eradication of enteric helicobacters in Mongolian gerbils is complicated by the occurrence of Clostridium difficile enterotoxemia
    Ingrid L Bergin
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Comp Med 55:265-8. 2005
    ..using dietary administration of antibiotics was complicated by the presence of toxin-producing C. difficile. An alternate method to develop helicobacter-free gerbils (such as Caesarian rederivation) may be necessary...
  28. pmc Cytolethal distending toxin is essential for Helicobacter hepaticus colonization in outbred Swiss Webster mice
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, 16 873, 77 Massachusetts Avenue, Cambridge, MA 02131, USA
    Infect Immun 73:3559-67. 2005
    ..hepaticus in cecum, colon, and jejunum but only transient colonization of H. hepaticus in the ileum of female mice; (iv) H. hepaticus colonization was associated with down-regulation of colonic IL-10 production...
  29. ncbi CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice
    Susan E Erdman
    Division of Comparative Medicine and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Res 65:3998-4004. 2005
    ..Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans...
  30. ncbi Identification of cholelithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation
    Kirk J Maurer
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Gastroenterology 128:1023-33. 2005
    ..To test this, we prospectively investigated the effects of Helicobacter spp infection in cholesterol gallstone pathogenesis in the highly susceptible C57L/J mouse model...
  31. ncbi A novel enterohepatic Helicobacter species 'Helicobacter mastomyrinus' isolated from the liver and intestine of rodents
    Zeli Shen
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Helicobacter 10:59-70. 2005
    ..A number of novel Helicobacter species have been isolated from both animals and humans. Many of these helicobacters colonize the lower gastrointestinal tract and hepatobiliary tract and are associated with diseases...
  32. ncbi Evaluation of Helicobacter hepaticus bacterial shedding in fostered and sex-segregated C57BL/6 mice
    Robin Crisler-Roberts
    Division of Laboratory Animal Medicine, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, Louisiana, USA
    Comp Med 55:515-22. 2005
    ..Our findings likely will prove useful in Helicobacter eradication efforts and in studies designed to further elucidate the role of H. hepaticus in disease...
  33. ncbi Thiol-reactive compounds prevent nonspecific antibody binding in immunohistochemistry
    Arlin B Rogers
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Lab Invest 86:526-33. 2006
    ..These findings provide a molecular basis to improve the specificity of IHC and other immunoassays, and hold implications for antibody-based clinical diagnostics and therapeutics...
  34. ncbi Detection, eradication, and research implications of Helicobacter infections in laboratory rodents
    Mark T Whary
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave, Bldg 16 825A, Cambridge, MA 02139, USA
    Lab Anim (NY) 35:25-7, 30-6. 2006
    ..The authors discuss the impact of subclinical and clinical disease and offer recommendations for managing helicobacter-free rodent colonies...
  35. pmc Inhibitory effect of enterohepatic Helicobacter hepaticus on innate immune responses of mouse intestinal epithelial cells
    Torsten Sterzenbach
    Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, 30625 Hannover, Germany
    Infect Immun 75:2717-28. 2007
    ..Suppression of innate immune responses by H. hepaticus LPS thus may affect intestinal responses to the resident microbial flora, epithelial homeostasis, and intestinal inflammatory conditions...
  36. ncbi Breast cancer: should gastrointestinal bacteria be on our radar screen?
    Varada P Rao
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cancer Res 67:847-50. 2007
    ....
  37. ncbi Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B
    Michal F Tomczak
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 177:7332-9. 2006
    ..These results suggest that the absence of the p50/p105 subunit of NF-kappaB within hemopoietic cells of the innate immune system interferes with the ability of IL-10 to suppress inflammatory gene expression and Hh-induced colitis...
  38. ncbi Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a baboon with pancreatic islet amyloidosis
    Alexis Garcia
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Med Microbiol 55:1591-5. 2006
    ..To the best of the authors' knowledge, this is the first report describing the isolation of enterohepatic Helicobacter species from a baboon...
  39. pmc Rapid onset of ulcerative typhlocolitis in B6.129P2-IL10tm1Cgn (IL-10-/-) mice infected with Helicobacter trogontum is associated with decreased colonization by altered Schaedler's flora
    M T Whary
    Division of Comparative Medicine, Massachusette Institute of Technology, 77 Massachusetts Avenue, Bldg 16 825A, Cambridge, MA 02139, USA
    Infect Immun 74:6615-23. 2006
    ..trogontum (with or without H. rodentium) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis...
  40. ncbi Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice
    Varada P Rao
    Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cancer Res 66:7395-400. 2006
    ..The possibility that dysregulated gut microbial infections in humans may lead to cancer in anatomically distant organs, such as breast, highlights the need for novel immune-based strategies in cancer prevention and treatment...
  41. pmc Colonization dynamics of altered Schaedler flora is influenced by gender, aging, and Helicobacter hepaticus infection in the intestines of Swiss Webster mice
    Zhongming Ge
    Division of Comparative Medicine, Massachusetts Institute of Technology, 16 873, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Appl Environ Microbiol 72:5100-3. 2006
    ..All ASF strains were detected in the cecum and colon, but some strains displayed significant variation in colonization levels with host age, gender, and H. hepaticus infection status...
  42. pmc Helicobacter anseris sp. nov. and Helicobacter brantae sp. nov., isolated from feces of resident Canada geese in the greater Boston area
    James G Fox
    Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg 16, Rm 825C, Cambridge, MA 02139, USA
    Appl Environ Microbiol 72:4633-7. 2006
    ..Whether these two novel helicobacters pose a zoonotic risk, similar to other enteric helicobacters (e.g., H. canadensis, previously isolated from diarrheic and bacteremic humans and from geese in Europe), will require further studies...
  43. pmc Probiotic Lactobacillus spp. diminish Helicobacter hepaticus-induced inflammatory bowel disease in interleukin-10-deficient mice
    Jeremy A Pena
    Department of Molecular Virology and Pathology, Baylor College of Medicine, 6621 Fannin St, Houston, TX 77030, USA
    Infect Immun 73:912-20. 2005
    ..In this H. hepaticus-challenged IL-10-deficient murine colitis model, lactobacilli demonstrated probiotic effects by direct modulation of mucosal inflammatory responses...