Intestinal dendritic cells: Their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men

Abstract

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota and food antigens. Dendritic cells (DC) generate primary T-cell responses, and determine whether these responses are immunogenic or tolerogenic. The regulatory role of DC is of particular importance in the gut due to the high antigenic load. Intestinal DC act as sentinels, sampling potentially pathogenic antigens but also harmless antigens including the commensal microbiota. Following antigen acquisition, intestinal DC migrate to secondary lymphoid organs to activate naive T-cells. DC also imprint specific homing properties on T-cells that they stimulate; gut DC specifically induce gut-homing properties on T-cells upon activation, enabling T-cell migration back to intestinal sites. Data regarding properties on gut DC in humans is scarce, although evidence now supports the role of DC as important players in intestinal immunity in humans. Here, we review the role of intestinal DC in shaping mucosal immune responses and directing tissue-specific T-cell responses, with a special focus on the importance of distinguishing DC subsets from macrophages at intestinal sites. We compare and contrast human DC with their murine counterparts, and discuss the ability of the gut microbiota to shape intestinal DC function, and how this may be dysregulated in inflammatory bowel disease (IBD). Lastly, we describe recent advances in the study of probiotics on intestinal DC function, including the use of soluble secreted bacterial products.