Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice

Abstract

How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.

Figure 1

Ontogenetic development of intestinal dendritic cells subpopulations. Adapted from Guilliams et al. [35] and expanded by findings from Scott et al. [13]. See text for details. Common dendritic cell progenitor (CDP), preplasmacytoid dendritic cell (pre-pDC), precommon dendritic cell (pre-cDC), plasmacytoid dendritic cell (pDC), common dendritic cell (cDC), aldehyde dehydrogenase (ALDH), regulatory T cell (Treg), retinoic acid (RA), and T-helper 17 cell (Th17). Arrows with solid lines represent published data, and arrows with broken lines represent speculative hypotheses with missing final evidence.

Figure 2

Possible molecular mechanisms of tolerance induction in intestinal dendritic cells. The white numbers in black circles refer to the numbering of regulation mechanisms in the text. See text for details.