Immune and inflammatory responses to Helicobacter pylori infection

The gastroduodenal response to chronic Helicobacter pylori infection is characterized by the infiltration of plasma cells, lymphocytes, neutrophils and monocytes into the mucosa. Eradication studies have shown that this inflammatory response represents a specific reaction to the presence of H. pylori. As well as stimulating specific local T and B cell responses and a systemic antibody response, H. pylori infection also induces a local pro-inflammatory cytokine response. Interleukin-8 (IL-8), which is expressed and secreted by gastric epithelial cells, may be an important host mediator inducing neutrophil migration and activation. IL-8 mRNA and protein secretion in gastric epithelial cell lines can be up-regulated by the cytokines tumour necrosis factor-alpha and IL-1 and also by type I strains of H. pylori (expressing the vacuolating toxin and cytotoxin-associated protein, CagA). The gastric epithelium thus plays an active role in mucosal defence. Neutrophil activation and the production of reactive oxygen metabolites will be induced directly by bacterial factors and indirectly via host-derived cytokines, products of complement activation and bioactive lipids. Strain variation in the induction of both IL-8 from epithelial cells and the oxidative burst in neutrophils may be an important factor determining the extent of mucosal injury. There is now increasing evidence from both in vivo and in vitro studies that type I strains induce an enhanced inflammatory response and mucosal damage. An understanding of the bacterial mediators of mucosal inflammation is important in elucidating the role of chronic H. pylori infection in the pathogenesis of gastroduodenal disease.