The role of the intracellular pathogen-recognition molecule Nod1 in the host response to Helicobacter pylori infection.

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The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected individuals develop inflammation of the stomach lining, yet only a proportion (15-20%) will go on to develop severe diseases, such as peptic ulcer disease and stomach cancer. Recent work from our groups has identified the mechanism by which H. pylori induces host responses in the cells lining the stomach, the epithelial cell. The interaction of the bacterium with these cells represents its first contact with the host, and sets the scene for the development of immune responses in the stomach. From their position on the outside surfaces of epithelial cells, certain strains of H. pylori are able to deliver a bacterial component into host cells, thus triggering an inflammatory response in the latter. Curiously, a host molecule called Nod1, which is present on the inside of cells and not on the surface, acts as an internal sensor by interpreting the entry of this H. pylori component as a danger signal for the host. The aim of the project will be to characterise the resulting defence mechanisms that are induced by Nod1 in order to prevent the colonisation of the stomach by H. pylori bacteria. It is expected that this work will address questions concerning the role of host immune defence mechanisms in H. pylori infection and stomach disease. Amongst the possible public health benefits of this work will be the development of novel therapies to reduce inflammation in the stomach by blocking Nod1 responses to H. pylori bacterial components.