Trends in Immunology
Research FocusHow do DCs interact with intestinal antigens?
Section snippets
Acquisition of antigens in the gut
The gut is exposed to multiple foreign antigens but is rarely goaded into damaging inflammatory responses. The anatomical location in which intestinal antigens are captured and the phenotype of the capturing cell are likely to have important implications for the nature of any immune response that develops. To maintain optimum intestinal function, it is crucially important that damaging inflammatory immune responses, vital for combating pathogenic organisms, are tightly controlled. Such
Trans-epithelial dendrites are generated in response to bacteria
Niess et al. [9] used a transgenic mouse in which the coding sequence of the fractalkine receptor gene (CX3CR1) had been replaced by a sequence expressing the green fluorescent protein (GFP). This permits direct visualization of DCs, which express the CX3CR1 molecule [10]. Heterozygous transgenic animals express one copy of each gene, thus CX3CR1-positive cells will fluoresce green. In this way, the authors could observe directly the transepithelial dendrites of CX3CR1-positive cells. All CD11b+
Dendrites are important for transport of non-invasive bacteria to mesenteric lymph nodes (MLNs)
Importantly, transepithelial dendrites seem to be responsible for much of the uptake of non-invasive bacteria into the lamina propria. DCs in the lamina propria of GFP–GFP (CX3CR1 null) animals have cellular processes that do not penetrate the epithelium: these are unable to transport non-invasive Escherichia coli to MLNs, whereas their PPs are still replete with bacteria. CX3CR1 expression therefore seems necessary for steady-state bacterial uptake into MLNs.
These data also suggest that PP DCs
Lamina propria DCs: tolerogenic, immunogenic or both?
In the steady state, presentation of antigens from the luminal flora leads to the generation of large quantities of antigen-specific IgA, without induction of systemic immunity. This IgA production requires the interaction of DCs with T and B cells in PPs, isolated lymphoid follicles and MLNs. T cell-mediated peripheral tolerance to intestinal flora, food and self-antigens is also maintained. However, in response to the recognition of pathogen-specific molecules, interactions among the
References (19)
Oral tolerance: immune mechanisms and the generation of Th3-type TGF-β-secreting regulatory cells
Microbes Infect.
(2001)Immunologic control of soluble protein absorption from the small intestine: a gut-surface phenomenon
Am. J. Clin. Nutr.
(1974)The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node
Immunity
(2005)Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity
Immunity
(2003)Anatomical basis of tolerance and immunity to intestinal antigens
Nat. Rev. Immunol.
(2003)A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes
J. Exp. Med.
(2000)- et al.
Intestinal epithelial antigen induces mucosal CD8 T cell tolerance, activation, and inflammatory response
J. Immunol.
(2004) IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut
J. Immunol.
(2004)Intestinal villous M cells: an antigen entry site in the mucosal epithelium
Proc. Natl. Acad. Sci. U. S. A.
(2004)
Cited by (34)
Probiotic application of beneficial bacteria for improved health and disease control
2023, Recent Advances in Aquaculture Microbial TechnologyThe Gastrointestinal Immune System
2018, Comprehensive Toxicology: Third EditionMucosal immunity in a healthy gut
2013, Diet, Immunity and InflammationThe role of the lymphatic system in vaccine trafficking and immune response
2011, Advanced Drug Delivery ReviewsCitation Excerpt :DCs residing in the mucosal epithelium of the gut generally have specialized surface properties that enable them to bind ingested antigens through their long processes. Microfold cells, sometimes referred to as M cells, also aid in transferring antigens present in the lumen of the gut or mucosal respiratory surfaces to the DCs residing in these environments [53]. Internalization of an antigen initiates a process through which the antigen is digested into smaller peptides within an acidic endosomal compartment and the resulting peptides are complexed with class I/II MHC molecules followed by upregulation of co-stimulatory molecules CD80 and CD86.
The gut as communicator between environment and host: Immunological consequences
2011, European Journal of PharmacologyCitation Excerpt :The subepithelial band of monocyte-derived CD103−CX3CR1+ DCs in the murine gut mucosa is indeed macrophage-like (Geissmann et al., 2010) and a source of IL-10 which contributes to expansion of Treg cells (Hadis et al., 2011). In a quiescent steady state, however, mucosal CD103+CCR7+ DCs (and possibly macrophages) are migratory and carry penetrating dietary and innocuous microbial antigens away from the gut mucosa to the MLNs (Bogunovic et al., 2009; Milling et al., 2005; Schulz et al., 2009; Worbs et al., 2006). Here a portion of the same cells, in a maturation process, becomes further conditioned for tolerance induction and drives the expansion of Treg cells (Brandtzaeg, 1998; Mowat, 2003).
The Gastrointestinal Immune System
2010, Comprehensive Toxicology, Second Edition