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Paul Kubes, University of Calgary Role of the Adapter Molecule MyD88 and the Protein Molecule TRIF in IBD About 10 years ago a number of scientists discovered how humans and other species recognize and respond to bacteria. Molecules called Toll-Like Receptors (TLRs) recognize and get our immune system to respond appropriately to pathogens. We live in harmony with many bacteria in our intestines that should also be recognized by these TLRs. However, they are somehow ignored, and white blood cells are not sent by TLRs to kill these bacteria. Based on this, it is reasonable to predict that if we could eliminate these TLRs in IBD patients, the inflammation would be reduced. Astoundingly, elimination of these proteins severely worsens IBD. For this reason, these receptors in the gut are suggested to be important in letting our immune system tolerate bacteria in the intestines. We have recently found a way to inhibit all 13 TLRs. We found that this leads to an unpredicted immune response that leads to chronic IBD. In just a few days, the response caused a chronic appearance of lymphocytes (a type of white blood cells), instead of the infiltration of neutrophils (another type of white blood cells) which is seen only in chronic IBD patients. The key may be an adaptor molecule called TRIF and a molecule protein called MyD88. Both molecules help the TLRs recognize bacteria. We will examine how these molecules play a role in causing severe IBD. Using a high-tech microscope, we can see how white blood cells enter the intestine. More importantly it allows us to identify each white blood cell. The type of white blood cell that is entering the intestines of severe IBD mice is different than in healthy situations or in situations where the IBD is moderate. We will use this microscopy to identify the mechanisms by which these white blood cells are getting in the intestine.