Mechanisms underlying the initiation of immunity in response to infection

Dendritic cells (DCs) and macrophages are critical cells in the gut for the initiation and control of immunity. Both DCs and macrophages act to help to maintain tolerance to harmless antigens such as food or commensal microbiota whilst initiating or enabling responses to pathogens. The gut is a major site of infection and diseases that affect millions worldwide yet comparatively little is known about how gut DCs and macrophages function in the switch from tolerance to activation. The gut is lined by a continuous epithelial barrier which must be breached for pathogens to attack. In the large intestine, we have observed a rapid recruitment of DCs to the gut epithelium which is strongly associated with resistance to many infectious diseases. The aim of this project is to define mechanisms involved in DC migration to the epithelium in infection and to determine how DCs and macrophages interact with the epithelium to initiate anti-pathogen immunity.