The disease spectrum of Helicobacter pylori: The immunopathogenesis of gastroduodenal ulcer and gastric cancer

Helicobacter pylori is a gram-negative bacterium that resides under microae robic conditions in a neutral microenvironment between the mucus and the su perficial epithelium of the stomach. From this site, it stimulates cytokine production by epithelial cells that recruit and activate immune and inflam matory cells in the underlying lamina propria, causing chronic, active gast ritis. Although epidemiological evidence shows that infection generally occ urs in children, the inflammatory changes progress throughout life. H. pylo ri has also been recognized as a pathogen that causes gastroduodenal ulcers and gastric cancer. These more severe manifestations of the infection usua lly occur later in life and in a minority of infected subjects. To interven e and protect those who might be at greatest risk of the more severe diseas e outcomes, it is of great interest to determine whether bacterial, host, o r environmental factors can be used to predict these events. To date, sever al epidemiological studies have attempted to define the factors affecting t he transmission of H. pylori and the expression of gastroduodenal disease c aused by this infection. Many other laboratories have focused on identifyin g bacterial factors that explain the variable expression of clinical diseas e associated with this infection. An alternative hypothesis is that microor ganisms that cause lifelong infections can ill afford to express virulence factors that directly cause disease, because the risk of losing the host is too great. Rather, we propose that gastroduodenal disease associated with H, pylori infection is predominantly a result of inappropriately regulated gastric immune responses to the infection. In this model, the interactions between the immune/inflammatory response, gastric physiology, and host repa ir mechanisms would dictate the disease outcome in response to infection.