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Research Project 4

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Intestinal Mucosal Immune and Functional Response to Gastric and Enteric Pathogens

This project is directed to take advantage of combined expertise in mucosal biology, proteomics, genomics, microbiomics, biochemistry, and molecular biology to determine the role of alterations in mucosal barrier function in host-microbial interactions affecting antigen trafficking that lead to local and systemic immune responses to gastric and enteric pathogens. These aims will be accomplished by investigating whether the mucosal response to exposure to H. pylori, S. Typhi (S. Typhimurium), or S. dysenteriae 1 influence antigen trafficking and epithelial immune responses using gastric, small, and large intestinal human and murine cell lines.

Moreover, these studies will attempt to establish the role of specific pattern recognition receptors (PRRs) in the gastrointestinal mucosal response to these pathogens using both wild type and knock out mice (Myd88, TLR4 and TLR5 KO) to study the effects of H. pylori, S. Typhi and S. dysenteriae 1 and their vaccine candidates on intestinal mucosal function and immune responses.

Finally, these studies will also attempt to define and characterize the gastrointestinal mucosal responses to H. pylori, S. Typhi and S. dysenteriae 1 in mucosal biopsies isolated from children, adults or elders undergoing diagnostic esophagogastroduodenoscopy for presumptive H. pylori infection (for more details, see Project 2), adults or elderly vaccinated with Ty21a (for more details, see Project 3), or non-human primates exposed to S. dysenteriae 1 or its vaccine candidate CVD 1256 (for more details, see Project 1).