Homeostatic Functions of Intestinal Macrophages

Macrophages (mϕ) are highly abundant in the healthy intestine, where they reside close to the epithelial layer and are thought to be important in preventing invasion by commensal bacteria and other microbes. We have shown recently that resident intestinal mϕ are replenished continuously by circulating monocytes that differentiate locally into ant-inflammatory cells characterised by high levels of CX3CR1, MHCII and IL10 production. Using microarray and phenotyping, we show here that maturing macrophages also acquire several scavenger receptors, tissue remodelling metalloproteases and receptors associated with clearance of apoptotic cells, including the αvβ5 integrin known to be crucial for clearance of effete rods and cones in the retina. Functional studies confirm that resident mϕ are highly phagocytic for both bacteria and apoptotic thymocytes in vitro. Epithelial cell derived cytokeratin could also be detected with mϕ isolated from normal colon. Together with the fact that mϕ are still present in germ free intestine, these data suggest that the antimicrobial scavenger functions of these cells may be secondary to a vital physiological role in maintaining intestinal tissue homeostasis and we are currently exploring the role of αvβ5 integrin in these processes.