Humans harbor 100 trillion intestinal bacteria that aid in digestion, promote immune system development, and protect against pathogen colonization. The Hooper lab studies the immune mechanisms that limit the ability of these resident bacteria to cross intestinal barriers and enter host tissues. To address these questions, we have established a germ-free mouse colony where mice are raised under completely sterile conditions inside plastic germ-free isolators. We are using germ-free mouse models to investigate the complex interactions that occur between intestinal bacteria and the immune system.
Our studies in germ-free mice have led to the discovery of a family of secreted C-type lectins that bind bacterial surface peptidoglycan and are directly bactericidal. Bacterial invasion of intestinal epithelia triggers lectin expression, which is critical for limiting bacterial contact with the intestinal surface. In ongoing work, we are using biochemical and structural approaches to understand how bactericidal intestinal lectins recognize their bacterial targets, and are also investigating the molecular mechanisms by which they kill bacteria. Finally, we are using genetically-engineered mouse models to determine how intestinal epithelial cells sense bacterial invasion and direct immune responses that limit bacterial access to deeper host tissues.
We use an integrated, multidisciplinary approach to address questions about intestinal host-microbial interactions. The approaches used in our lab range from biochemical and structural approaches for understanding antimicrobial protein function to mouse genetic approaches for determining how intestinal immune cells detect and respond to intestinal bacteria. Together our aim is to obtain a detailed, mechanistic understanding of how the immune system copes with enormous numbers of symbiotic intestinal bacteria.
Our work is funded by the Howard Hughes Medical Institute, the National Institutes of Health, the Burroughs Wellcome Foundation, the Crohns and Colitis Foundation, and the Welch Foundation.