title: Helicobacter pylori infection: pathogenesis.
abstract: Helicobacter pylori is known to be the cause of most gastric diseases, including both peptic ulcer disease and gastric cancer. In the absence of eradication, infection tends to be lifelong and the immune response ineffective in clearing the bacteria. A number of groups have investigated whether the immune clearance of infection can be achieved through a vaccination strategy, but to date, the results have been inconclusive. In fact, in most cases of natural infection, the host immune response leads to a chronic inflammation within the gastric mucosa that actually promotes the development of atrophy and neoplasia. In most cases, eradication of the organism leads to resolution of inflammation, which in many instances can result in reduction in atrophy and gastric cancer risk. This finding suggests that even at late stages, cancer progression is dependent, to a large extent, on infection/immune response. Work from a number of laboratories has led to the hypothesis that T-cells and the Th1 immune response, governed largely by host genetic factors, are strongly associated with the H. pylori-mediated induction of atrophy and cancer. Interleukin-1beta appears to be a particularly important cytokine that inhibits acid secretion and increases serum gastrin levels, factors strongly associated with cancer induction. The induction by H. pylori of cytokines and chemokines and growth-related genes is mediated by the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF-kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1 pathway. H. pylori can also promote cellular apoptosis through a number of mechanisms, the most important of which is upregulation of the Fas/FasL pathway. Finally, understanding of H. pylori pathogenesis has been broadened and deepened by the application of genomics and proteomics to the organism.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. jgfox@mit.edu
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang