Infection with Helicobacter pylori causes a histological gastritis that in some individuals is associated with the development of peptic ulcer disease or gastric malignancy. H. pylori infection may be more common than infection with any other bacterial agent. Yet despite what must be repeated exposures, some individuals do not become infected. What accounts for the fact that some individuals become persistently infected while others remain uninfected, and perhaps still others have a transient infection? Presumably, bacterial as well as host variables are important. Because experimental infection of humans with H. pylori is not possible, the investigators propose to use the rhesus monkey as a model of H. pylori infection to address this question. They hypothesize that inoculation of human H. pylori in rhesus monkeys will result in diverse outcomes that will be associated with conditions of bacterial inoculation as well as host variables. A type strain of human H. pylori will be selected by in vitro characterization and in vivo passage through rhesus monkeys. The effects on infection of inoculum size, gastric acid suppression, and bacterial growth phase will be examined. Animals will be orogastrically inoculated with a standard dose of the type strain and acute and chronic infection will be studied. The outcome of infection will be determined by serial endoscopy, urea breath test, and examination of bacterial shedding in saliva and feces by culture and PCR. The host immune response will be assessed by immunophenotyping of gastric lymphocytes and peripheral blood mononuclear cells, immunohistochemistry of gastric mucosal inflammation, T cell proliferative responses from peripheral blood and gastric mucosa, and cytokine secretion by T cells. Gastric physiology will be examined by assay of serum gastrin levels and gastric basal acid output. The results will be compared in juvenile and adult animals. These studies will further understanding of the host-pathogen relationship in acute and chronic H. pylori infection.
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