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

1982年，两位澳大利亚临床医生马歇尔博士和沃伦博士发表了一份关于螺旋形细菌幽门螺杆菌与人类胃病之间联系的报告，这被证明是过去二三十年医学研究的突破性发现之一。尽管此后进行了广泛的研究，包括对两种不同的幽门螺杆菌分离株的全基因组测序，但与幽门螺杆菌疾病有关的许多问题仍未得到解答。例如，目前尚不清楚为什么所有受感染的人都会患上胃粘膜炎症，但只有一部分人（15-20%）会发展成严重的疾病，如消化性溃疡和胃癌。我们小组最近的工作已经确定了幽门螺旋杆菌在胃粘膜细胞，上皮细胞中诱导宿主反应的机制。细菌与这些细胞的相互作用代表了它与宿主的第一次接触，并为胃中免疫反应的发展奠定了基础。某些幽门螺杆菌菌株位于上皮细胞的外表面，能够将细菌成分传递到宿主细胞中，从而引发宿主细胞的炎症反应。奇怪的是，一种名为Nod1的宿主分子存在于细胞内部而不是表面，它充当了一个内部传感器，将这种幽门螺旋杆菌成分的进入解读为宿主的危险信号。该项目的目的是描述由Nod1诱导的防御机制，以防止幽门螺杆菌在胃中定植。期望这项工作将解决宿主免疫防御机制在幽门螺杆菌感染和胃病中的作用问题。这项工作可能对公共卫生有好处，其中包括开发新的治疗方法，通过阻断Nod1对幽门螺杆菌细菌成分的反应来减少胃部炎症。

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.