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. 1996 Jan;64(1):238–245. doi: 10.1128/iai.64.1.238-245.1996

Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis infection of inbred and congenic mouse strains.

M Mohammadi 1, R Redline 1, J Nedrud 1, S Czinn 1
PMCID: PMC173751  PMID: 8557346

Abstract

In humans, Helicobacter pylori establishes a chronic infection which can result in various degrees of gastric inflammation, peptic ulcer disease, and a predisposition to gastric cancer. It has been suggested that bacterial virulence factors such as the vacuolating toxin (VacA) and the cytotoxin-associated gene product (CagA) may play a major role in determining the clinical outcome of Helicobacter infections. The role of host responses in these varied outcomes has received little attention. Helicobacter felis, which does not express CagA or VacA, causes chronic infection and inflammation in a well-characterized mouse model. We have used this model to evaluate the role of host responses in Helicobacter infections. BALB/c, C3H, and C57BL/6 mice were orally infected with a single strain of H. felis, and 2 and 11 weeks after infection, the mice were sacrificed and evaluated histologically for magnitude of H. felis infection. Intensity and extent of inflammation, and cellular composition of the inflammatory infiltrate. All three strains of mice demonstrated comparable levels of infection at 11 weeks, but the pattern and intensity of inflammation varied from minimal in BALB/c mice to severe in C57BL/6 mice. Gastric epithelial erosions were noted in C3H mice, and mucous cell hyperplasia was observed in C3H and C57BL/6 mice. Abundant mucosal mast cells were observed in the gastric tissues of all three mouse strains. Studies using major histocompatibility complex (MHC)-congenic mice revealed probable contributions by both MHC and non-MHC genes to Helicobacter-induced inflammation. Thus, large variations in the severity of disease were observed after infection of different inbred strains and congenic mice with a single isolate of H. felis. These results demonstrate the importance of the host response in disease outcome following gastric Helicobacter infection.

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Selected References

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  1. An international association between Helicobacter pylori infection and gastric cancer. The EUROGAST Study Group. Lancet. 1993 May 29;341(8857):1359–1362. [PubMed] [Google Scholar]
  2. Azuma T., Konishi J., Tanaka Y., Hirai M., Ito S., Kato T., Kohli Y. Contribution of HLA-DQA gene to host's response against Helicobacter pylori. Lancet. 1994 Feb 26;343(8896):542–543. doi: 10.1016/s0140-6736(94)91496-6. [DOI] [PubMed] [Google Scholar]
  3. Blanchard T. G., Czinn S. J., Maurer R., Thomas W. D., Soman G., Nedrud J. G. Urease-specific monoclonal antibodies prevent Helicobacter felis infection in mice. Infect Immun. 1995 Apr;63(4):1394–1399. doi: 10.1128/iai.63.4.1394-1399.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanchard T. G., Czinn S. J., Nedrud J. G., Redline R. W. Helicobacter-associated gastritis in SCID mice. Infect Immun. 1995 Mar;63(3):1113–1115. doi: 10.1128/iai.63.3.1113-1115.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen M., Lee A., Hazell S., Hu P., Li Y. Immunisation against gastric infection with Helicobacter species: first step in the prophylaxis of gastric cancer? Zentralbl Bakteriol. 1993 Sep;280(1-2):155–165. doi: 10.1016/s0934-8840(11)80952-7. [DOI] [PubMed] [Google Scholar]
  6. Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z., Figura N. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5791–5795. doi: 10.1073/pnas.90.12.5791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cover T. L., Cao P., Lind C. D., Tham K. T., Blaser M. J. Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. Infect Immun. 1993 Dec;61(12):5008–5012. doi: 10.1128/iai.61.12.5008-5012.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Czinn S. J., Cai A., Nedrud J. G. Protection of germ-free mice from infection by Helicobacter felis after active oral or passive IgA immunization. Vaccine. 1993;11(6):637–642. doi: 10.1016/0264-410x(93)90309-l. [DOI] [PubMed] [Google Scholar]
  9. Dewhirst F. E., Seymour C., Fraser G. J., Paster B. J., Fox J. G. Phylogeny of Helicobacter isolates from bird and swine feces and description of Helicobacter pametensis sp. nov. Int J Syst Bacteriol. 1994 Jul;44(3):553–560. doi: 10.1099/00207713-44-3-553. [DOI] [PubMed] [Google Scholar]
  10. Dick-Hegedus E., Lee A. Use of a mouse model to examine anti-Helicobacter pylori agents. Scand J Gastroenterol. 1991 Sep;26(9):909–915. doi: 10.3109/00365529108996241. [DOI] [PubMed] [Google Scholar]
  11. Eaton K. A., Radin M. J., Krakowka S. Animal models of bacterial gastritis: the role of host, bacterial species and duration of infection on severity of gastritis. Zentralbl Bakteriol. 1993 Sep;280(1-2):28–37. doi: 10.1016/s0934-8840(11)80938-2. [DOI] [PubMed] [Google Scholar]
  12. Fox J. G., Blanco M., Murphy J. C., Taylor N. S., Lee A., Kabok Z., Pappo J. Local and systemic immune responses in murine Helicobacter felis active chronic gastritis. Infect Immun. 1993 Jun;61(6):2309–2315. doi: 10.1128/iai.61.6.2309-2315.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fox J. G., Lee A., Otto G., Taylor N. S., Murphy J. C. Helicobacter felis gastritis in gnotobiotic rats: an animal model of Helicobacter pylori gastritis. Infect Immun. 1991 Mar;59(3):785–791. doi: 10.1128/iai.59.3.785-791.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gervais F., Stevenson M., Skamene E. Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus. J Immunol. 1984 Apr;132(4):2078–2083. [PubMed] [Google Scholar]
  15. Greiner A., Marx A., Heesemann J., Leebmann J., Schmausser B., Müller-Hermelink H. K. Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis. Lab Invest. 1994 Apr;70(4):572–578. [PubMed] [Google Scholar]
  16. Karita M., Kouchiyama T., Okita K., Nakazawa T. New small animal model for human gastric Helicobacter pylori infection: success in both nude and euthymic mice. Am J Gastroenterol. 1991 Nov;86(11):1596–1603. [PubMed] [Google Scholar]
  17. Karita M., Li Q., Cantero D., Okita K. Establishment of a small animal model for human Helicobacter pylori infection using germ-free mouse. Am J Gastroenterol. 1994 Feb;89(2):208–213. [PubMed] [Google Scholar]
  18. Kurose I., Granger D. N., Evans D. J., Jr, Evans D. G., Graham D. Y., Miyasaka M., Anderson D. C., Wolf R. E., Cepinskas G., Kvietys P. R. Helicobacter pylori-induced microvascular protein leakage in rats: role of neutrophils, mast cells, and platelets. Gastroenterology. 1994 Jul;107(1):70–79. doi: 10.1016/0016-5085(94)90062-0. [DOI] [PubMed] [Google Scholar]
  19. Lee A., Chen M., Coltro N., O'Rourke J., Hazell S., Hu P., Li Y. Long term infection of the gastric mucosa with Helicobacter species does induce atrophic gastritis in an animal model of Helicobacter pylori infection. Zentralbl Bakteriol. 1993 Sep;280(1-2):38–50. doi: 10.1016/s0934-8840(11)80939-4. [DOI] [PubMed] [Google Scholar]
  20. Lee A., Fox J. G., Otto G., Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology. 1990 Nov;99(5):1315–1323. doi: 10.1016/0016-5085(90)91156-z. [DOI] [PubMed] [Google Scholar]
  21. Malaty H. M., Engstrand L., Pedersen N. L., Graham D. Y. Helicobacter pylori infection: genetic and environmental influences. A study of twins. Ann Intern Med. 1994 Jun 15;120(12):982–986. doi: 10.7326/0003-4819-120-12-199406150-00002. [DOI] [PubMed] [Google Scholar]
  22. Malo D., Skamene E. Genetic control of host resistance to infection. Trends Genet. 1994 Oct;10(10):365–371. doi: 10.1016/0168-9525(94)90133-3. [DOI] [PubMed] [Google Scholar]
  23. Marchetti M., Aricò B., Burroni D., Figura N., Rappuoli R., Ghiara P. Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science. 1995 Mar 17;267(5204):1655–1658. doi: 10.1126/science.7886456. [DOI] [PubMed] [Google Scholar]
  24. Marshall B. J., Armstrong J. A., McGechie D. B., Glancy R. J. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Med J Aust. 1985 Apr 15;142(8):436–439. doi: 10.5694/j.1326-5377.1985.tb113443.x. [DOI] [PubMed] [Google Scholar]
  25. Michetti P., Corthésy-Theulaz I., Davin C., Haas R., Vaney A. C., Heitz M., Bille J., Kraehenbuhl J. P., Saraga E., Blum A. L. Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease. Gastroenterology. 1994 Oct;107(4):1002–1011. doi: 10.1016/0016-5085(94)90224-0. [DOI] [PubMed] [Google Scholar]
  26. Morris A., Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987 Mar;82(3):192–199. [PubMed] [Google Scholar]
  27. Nawa Y., Ishikawa N., Tsuchiya K., Horii Y., Abe T., Khan A. I., Bing-Shi, Itoh H., Ide H., Uchiyama F. Selective effector mechanisms for the expulsion of intestinal helminths. Parasite Immunol. 1994 Jul;16(7):333–338. doi: 10.1111/j.1365-3024.1994.tb00358.x. [DOI] [PubMed] [Google Scholar]
  28. Pappo J., Thomas W. D., Jr, Kabok Z., Taylor N. S., Murphy J. C., Fox J. G. Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis. Infect Immun. 1995 Apr;63(4):1246–1252. doi: 10.1128/iai.63.4.1246-1252.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Plant J., Glynn A. A. Genetics of resistance to infection with Salmonella typhimurium in mice. J Infect Dis. 1976 Jan;133(1):72–78. doi: 10.1093/infdis/133.1.72. [DOI] [PubMed] [Google Scholar]
  30. Solnick J. V., O'Rourke J., Lee A., Paster B. J., Dewhirst F. E., Tompkins L. S. An uncultured gastric spiral organism is a newly identified Helicobacter in humans. J Infect Dis. 1993 Aug;168(2):379–385. doi: 10.1093/infdis/168.2.379. [DOI] [PubMed] [Google Scholar]
  31. Telford J. L., Ghiara P., Dell'Orco M., Comanducci M., Burroni D., Bugnoli M., Tecce M. F., Censini S., Covacci A., Xiang Z. Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J Exp Med. 1994 May 1;179(5):1653–1658. doi: 10.1084/jem.179.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tytgat G. N., Rauws E. A. Campylobacter pylori and its role in peptic ulcer disease. Gastroenterol Clin North Am. 1990 Mar;19(1):183–196. [PubMed] [Google Scholar]
  33. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983 Jun 4;1(8336):1273–1275. [PubMed] [Google Scholar]
  34. Xiang Z., Censini S., Bayeli P. F., Telford J. L., Figura N., Rappuoli R., Covacci A. Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect Immun. 1995 Jan;63(1):94–98. doi: 10.1128/iai.63.1.94-98.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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