Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses

Abstract

Mammals coexist in an overall symbiotic relationship with a complex array of commensal bacterial flora that colonizes the gastrointestinal tract. These intestinal bacteria interface with cells of the mucosal immune system, including DCs. Here we discuss mechanisms of interaction between intestinal bacteria and DCs and the role of localized gastrointestinal immune responses.

Figure 1

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.

Figure 2

Specialized commensal bacteria occupy niches in different compartments of the GIT. The structure of the murine intestine in different parts of the GIT most certainly reflects its dominant purpose of digesting and absorbing nutrients. However, the presence and usage of various immune-response mechanisms also mirror the interplay with the respective resident intestinal bacteria in compartments that these bacteria are adapted to colonize as a permanent or temporary ecological niche. The immune response, in return, can shape the commensal bacterial flora (15). Whereas the total bacterial load increases toward the lower GIT, distinct bacteria are adapted to predominantly colonize niches in the small intestine or cecum (refs. , ; and M. Strus et al., unpublished observations). Original magnification of the micrographs, ×200. spp., species.