Pathways for the Recognition of the Intestinal Microbiota

Abstract

The specific role of most of these newly discovered DC subsets in antigen sampling and presentation is unknown and it remains therefore unclear whether they work synergistically, as alternatives or have distinct functions in the recognition of the intestinal microbiota. The focus of effort in this field will be to understand how these diverse DC subsets cooperate in regulating the complex homeostasis and host defense in the different intestinal immune compartments. The intestinal lamina propria contains a DC network that serves as a newly discovered gateway for the uptake and transport of the intestinal microbiota. Specialized vesicular structures at the end of transepithelial dendrites serve as 'luminal sensors' for the mucosal immune system. Characterization of the surface components of these luminal sensors may aid in developing strategies to prevent bacterial and viral pathogen entry. We propose that the lamina propria and M cell-dependent antigen sampling systems are associated with specific DC subsets. The discovery of functionally defined subsets of dendritic cells associated with distinct mechanisms responsible for the uptake of antigens across the intestinal barrier opens the path for strategies for targeting them specifically in the development of vaccines or treatment approaches for inflammatory bowel diseases. For these exciting possibilities to progress into practical applications, it needs to be established whether distinct DCs subsets are associated with multiple pathways or if their function is linked to specific innate or adaptive immune responses. Defining DC function in the intestine will be pivotal in finally progressing our understanding on how the mucosal immune system makes the distinction between commensal microbiota, pathogens and self antigens.