Elucidating Intestinal Macrophage Biology. (360G-Wellcome-088174_Z_09_Z)

There are large numbers of macrophages in the normal large intestine, positioned immediately under the epithelium and the commensal microbiota. Although these resident macrophages are actively phagocytic and bactericidal, most do not express toll like receptors or produce inflammatory cytokines. Thus they may contribute to intestinal homeostasis by limiting penetration of commensal organisms without causing inflammation. Recognition of microbial products by macrophages also controls epithelial i ntegrity in the healthy intestine, while activated intestinal macrophages play a central role in protective immunity against pathogens. Macrophages are also important effector cells in inflammatory bowel diseases (IBD), with the appearance of a dominant subset of TLR-expressing, cytokine producing macrophages. Our recent work shows that a few TLR+ macrophages are also present in normal colon and it is unclear how all these apparently distinct properties are controlled, nor is it known if the re sident and inflammatory subsets represent distinct lineages of macrophage which are recruited differentially in health and disease, or if they reflect alternative differentiation of the same lineage. This sabbatical will allow Professor Mowat to acquire flow cytometric methods and skills available at the University of Lund which will allow these issues to be addressed in animal models used in Glasgow.