Host response and vaccine development to Helicobacter pylori infection

Abstract

Studies in both humans and animals demonstrate that H. pylori is capable of illiciting an innate response that in part is regulated by the genetic makeup of the host. These innate responses includes stimulating immune effector mechanisms at the cellular and biochemical level resulting in the influx of neutrophils into the lamina propria and have even been shown to modify gastric acid secretion. The availability of good animal models of chronic Helicobacter infection has also allowed investigators to begin to examine how the adaptive host immune response prevents and/or exacerbates Helicobacter-induced gastroduodenal disease. The experimental H. felis/mouse model has been utilized by a number of laboratories to investigate mechanisms of host defense against chronic Helicobacter infection. This model and the more recently developed H. pylori rodent model has not only allowed investigators to confirm the feasibility of immunotherapy to prevent and/or cure Helicobacter infection but also to begin to examine how the host immune response prevents and/or exacerbates Helicobacter-induced gastroduodenal disease. Based on these studies a hypothesis is emerging that suggests that protection and/or cure from Helicobacter infection is mediated primarily by an upregulated cellular immune response which may act via an antibody independent mechanism. Paradoxically, following natural infection with H. pylori, a component of the cellular immune response also promotes chronic gastric inflammation without clearance of the organism. The recent development of reliable and reproducible H. pylori/rodent models of disease and the availability of numerous inbred strains, transgenic and knockout animals, will allow investigators to continue to explore the role the host cellular and humoral immune response plays in promoting or preventing this infection.