This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: Helicobacter pylori causes an inflammatory infiltrate in gastric mucosa that in about 10% of cases progresses to peptic ulcer disease or gastric cancer. Disease results from an interaction between strain-specific bacterial virulence genes and the particular host response, neither of which is well understood. Since experimental inoculation of rhesus macaques with H. pylori causes gastritis that closely mimics human infection, this model provides a unique opportunity to further our understanding of H. pylori pathogenesis. Rapid progress in genomics and gene expression technologies makes it possible to use the macaque model to study the H. pylori host-pathogen interaction by in vivo analysis of gene expression. We propose to extend our work in the rhesus model of H. pylori into an analysis of bacterial (Specific Aim 1) and host (Specific Aim 2) gene expression during experimental infection. Since the host immune response is increasingly recognized as a critical variable in the outcome of infection, we will also study host gene transcription after immunization with urease coupled with either CpG or alum adjuvant, in order to promote a Th1 or Th2 immune response, respectively (Specific Aim 3). These studies will provide a functional genomic understanding of the H. pylori host-pathogen relationship that may have implications for novel treatment or vaccine strategies.
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