Mucosal Immunology

Scope

This program is investigating the interactions between pathogenic organisms and the host mucosal surface.

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

Research outline

Helicobacter infections and immune tolerance

Phil Sutton and Stacey Harbour

Infection of humans with Helicobacter pylori produces a chronic gastritis that in some people can lead to the development of peptic ulcers, Mucosal-Associated Lymphoid Tissue (MALT) lymphoma and gastric adenocarcinoma. Some infected individuals develop serious pathologies while most remain asymptomatic due to a variety of different factors, including bacterial strain variation and diet. Another key factor is host genetics which may, for example, influence the immune response mounted against infection.

Infection of the majority of mice with 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.

Mucosal and systemic responses to vaccines

Jean-Pierre Scheerlinck, Hung-Hsun Yen, Janet Wee and Phil Sutton

Sheep are used as a model for both ruminants and humans to complement studies performed in small rodents. Lymphatic cannulation of individual lymph nodes can easily be performed in sheep and allows access to immune cells and mediators very close to the site of immunisation. Cannulation of lymph nodes draining different organs and tissue compartments allows dissection of the initial events leading to induction of mucosal or peripheral immune responses following different immunization procedures. Cannulation of the duct draining the prefemoral lymph node allows for the charactersation of the immune response following subcutaneous and intradermal vaccination, while cannulation of the tracheal lymph trunks allows for the characterisation of vaccine delivered via the intra-nasal route. Thus local immune responses to vaccination using different routes of immunization and delivery systems are being compared.

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

Role of mucus in immune protection

Phil Sutton and Jean-Pierre Scheerlinck

The mucosal surface is coated with a “glycocalyx” consisting predominantly of mucin glycoproteins and mucus. The role of these mucins in host-pathogen interactions has never properly been investigated. Recently the Centre for Animal Biotechnology was a co-founder of a consortium of Australian institutes, formed to address this issue. Thus, this program is being undertaken in collaboration with the Mater Medical Research Institute in Brisbane, The Austin Research Institute in Melbourne and The Institute for Glycomics on the Gold Coast. This consortium has been named Australian Research in Mucosal Defence (ARMD).

The research within this program that occurs at The Centre for Animal Biotechnology focuses on mouse helicobacter modelswhich are being used to investigate host-pathogen interactions in the 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.
• Scheerlinck J-P. Y., S. Gekas, H-H. Yen, S. Edwards, M. Pearse, A. Coulter and P. Sutton (2006). Draining immune response following nasal delivery of an adjuvanted influenza vaccine. Vaccine 24: 3929-3936
• Yen H-H., J-P. Y. Scheerlinck, S. Gekas and P. Sutton (2006) A Sheep Cannulation Model for Evaluation of Nasal Vaccine Delivery. Methods 38: 117-123.
• Sutton P. & Doidge C. (2003) Helicobacter pylori vaccines spiral into the new millennium. Digestive and Liver Disease. 35: 675-687.
• 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: 467-47.
• 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., 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.