How do intestinal DCs sense the bacterial flora? Current theories of how DCs come into contact with the intestinal bacterial flora can be divided into those that propose an active sampling of bacteria by the host (I and II) and those that involve DCs acting as antigen-sampling cells when bacteria have already crossed the epithelial barrier (III and IV). M cells as specialized epithelial cells can mediate the uptake of bacteria toward DCs in the intestinal lymphoid tissue (I) (13). This mechanism can be exploited as an entry site by pathogens. In addition, it has been shown that DCs can reach through the basal membrane and the epithelial layer toward the lumen via dendrites (II) (21). In this case, DCs express the tight junction proteins occludin, claudin 1, and zonula occludens 1, by which they can keep the barrier integrity intact (21). DCs may also sample translocated bacteria that reach the lamina propria because of a low degree of physiological leakiness of the epithelium (III), and they might contribute to the clearance of pathogenic bacteria that reach the lamina propria via invasion and/or tissue damage (IV). Becker et al. describe a population of DCs in the crypt lamina propria of the terminal ileum that produce IL-23 and contain bacteria (9). Whether these DCs actively sample bacteria from the crypt lumen or respond to invasive bacteria is currently not understood. After antigen encounter, DCs travel in local lymphoid structures such as Peyer’s patches (PP) and toward the draining mesenteric lymph nodes (MLN) to initiate or maintain T and B cell immune responses.