Campylobacter pylori is a newly described gram-negative bacterial organism suspected of having a causal role in the development of human gastroduodenal disease, namely gastritis and peptic ulcer. Delineation of its role in gastritis is hampered by the inability to induce gastric infection in conventional laboratory animal species. In preliminary studies, we have shown the C. pylori will infect gastric mucosa of neonatal gnotobiotic piglets. Thus, the overall goal of the proposed research is to exploit this observation towards elucidation of the pathology, immunology, physiology and microbiology of gastric disease in piglets. The core of our proposed research centers around the conduction of a long- term (120 days) study in conventionalized piglets infected with C. pylori as gnotobiotes. Before initiating this experiment, we will first develop an endoscopy procedure to facilitate repeated examination of infected gastric mucosa. Secondly, we will fully characterize local and systemic humoral and cellular immune responses in infected piglets and determine the consequences of infection upon selected parameters of gastric physiology. One these techniques are mastered we will determine the role of selected bacterial virulence factors (urease and motility) in the pathogenesis of gastritis in a series of short-using developed endoscopic, immunologic and physiologic monitoring procedures. Finally, we will conduct an immunization-re-infection study to determine if pre-existent immunity inhibits re-colonization and subsequent gastritis in piglets. These data will establish the significance of C. pylori in gastric disease and will provide a nonprimate animal model for further studies of the biology of this agent.
