Center for Animal Biotechnology  CAB : Helicobacter
 
CENTRE FOR ANIMAL BIOTECHNOLOGY  

Helicobacter infections

Scope

The Immunology and Mucosal Pathogens research group has a major focus on investigating factors involved in the infection and pathogenesis of Helicobacter species as well as working on the development of a vaccine against H. pylori.

Research outline

Helicobacter pylori infects the stomachs of half the World's population and is a major cause of peptic ulcer disease (both gastric and duodenal ulcers) plus two types of cancer, MALT lymphoma and gastric adenocarcinoma. Gastric adenocarcinoma is the second most common cause of death due to cancer. In addition to H. pylori there are a multitude of other Helicobacter species which infect and are pathogenic in humans, as well as in sheep, cats, dogs and possibly many other animals.

Helicobacter pylori vaccines

A prophylactic vaccine against H. pylori would be of great benefit in protecting against the development of these diseases, while a therapeutic vaccine would be of benefit to individuals in whom antimicrobial therapy fails to clear infection. Current vaccine strategies have not been successful, failing to produce sterilising protection in mice and even less effective in humans. We are currently investigating approaches aimed (i) at improving the efficiencies of these vaccinations and (ii) to identify novel antigenic targets.

 

Helicobacter project staff: From left to right: Janet Wee (post-doc), Agi Swierczak (RA), Stacey Harbour (PhD student), Phil Sutton (Group leader), Caroline Skene (PhD student), Alison Every (Post-doc), Teng Chionh (PhD student).


The body of a normal (left) and Helicobacter-Induced Gastritis (right) mouse stomach stained with Alcian Blue and Periodic Acid Schiff (AB-PAS).

Helicobacter Pathogenesis

Infection of humans with H. pylori produces a chronic gastritis that in some people can lead to the development of the associated pathologies. While some infected individuals develop serious pathologies others remain asymptomatic. This variability is due to a variety the complex interaction of different factors, including bacterial strain variation , diet and diet. Another key factor is the genetic makeup of the infected host genetics, which can heavily influence the immune response mounted against infection.
The IMP group is very interested in understanding the mechanisms of pathogenesis of Helicobacter infection. In particular we are examining the role of host genetic factors in regulating the severity of inflammation induced in response to these infections. Infection of the majority of mice with gastric Helicobacter also produces chronic gastritis. We have developed a model of Helicobacter infection where mice do not develop gastritis and this trait is dominantly inherited in offspring. Using this model we are studying the types of immune cells and mucosal mechanisms that regulate inappropriate immune responses to gastrointestinal infections and that are involved in the induction of immune tolerance. In addition, we are examining the impact of gender effects and the expression of mucins in the gastric mucosa on host susceptibility to Helicobacter-associated pathogenesis.


Helicobacter pylori (left) and H. felis (right). Electron Micrographs courtesy of Lucy Thompson, school of Biotechnology & Biomolecular Sciences, University of New South Wales.

Helicobacter Colonisation

Another tier of our research involves examining factors associated with colonisation – i.e. what is important for the bacteria to infect the host’s stomach. In this regard we are examining the importance of glycosylation of both the bacteria and the host, in particular with regard to the highly glycosylated mucins which line the mammalian stomach.

 


Key publications

  • McGuckin M, Every A, Skene C, Linden S, McAuley J, Swierczak A, Harbour S, Kaparakis M, Ferrero R & Sutton P. (2007) Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis. Gastroenterology 133: 1210-1218.
  • Skene C & Sutton P. (2006) Saponin-adjuvanted particulate vaccines for clinical use. Methods [In Press]
  • Sutton P. , O'Rourke J., Wilson J., Dixon M.F. & Lee A. (2004) Immunisation against Helicobacter felis infection protects against the development of gastric MALT lymphoma. Vaccine 22: 2541-2546.
  • Mueller A., O'Rourke J., Chu P., Kim C., Sutton P. , Lee A. & Falkow S. (2003) Protective immunity against Helicobacter is characterized by a unique transcriptional signal. Proc Nat Acad Sci 100 : 12289-12294.
  • Sutton P. , Danon, S., Walker M., Thompson, L., Wilson J., Kosaka T. & Lee A. (2001) Post-immunisation gastritis and Helicobacter infection in the mouse: A long term study. Gut 49: 467-473.
  • Sutton P. (2001) Helicobacter pylori vaccines and mechanisms of effective immunity: Is mucus the key? Immunology and Cell Biology 79 : 67-73.
  • Sutton P, Kolesnikow T, Danon S, Wilson J & Lee A. (2000) Dominant non-responsiveness to Helicobacter pylori infection is associated with production of Interleukin 10 but not Interferon g. Infection and Immunity 68: 4802-4804.
  • Sutton P. , Wilson J. & Lee A. (2000) Further development of the Helicobacter pylori mouse vaccination model. Vaccine 18 : 2677-2685.
  • Sutton P. , Wilson J., Kosaka T., Wolowczuk I. & Lee A. (2000) Therapeutic immunisation against Helicobacter pylori infection in the absence of antibodies. Immunology and Cell Biology 78 : 28-30.
  • Sutton P, Wilson J, Genta R, Pappo J, Torrey D, Savinainen A & Lee A. (1999) A genetic basis for atrophy: dominant non-responsiveness and Helicobacter-induced gastritis in F1 hybrid mice. Gut 45: 335–340.
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