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Interactions between dendritic cells and bacteria in the regulation of intestinal immunity

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Abstract

Dendritic cells (DCs) are immunoregulatory antigen-presenting cells. DCs can be potent activators of naı̈ve T cells and influence the generation and homing of effector lymphocytes; they can also induce regulatory mechanisms and maintain non-responsiveness. In part, these different outcomes are influenced by exposure of the DC to microbial products. The regulatory role of DCs is of particular importance at mucosal surfaces such as the intestine, where the immune system exists in intimate association with the external antigenic environment. Much of what we know about DCs has come from studies on the cells outside the gastrointestinal tract but information about gut DCs and their contribution to the specialized immune environment of the gut is now emerging. Here, we review current knowledge on gut DCs, suggest models for interactions between DCs and the commensal microflora in health and disease, and discuss gut DCs as targets for probiotic therapies.

Section snippets

Dendritic cell biology

Two aspects are central to the role played by the DC: the acquisition of antigen and the stimulation of lymphocytes. Usually antigen acquisition occurs in peripheral tissues, as opposed to central lymphoid tissues. In these peripheral sites it is ‘immature’ DCs, present in small numbers, that take up antigen directly or via antigen-bearing non-APCs, including apoptotic cells. This enables antigens that are normally restricted to non-haemopoietic types of cell to stimulate an immune response.1

Control of immune responses by DCs

A number of factors influence which of the possible outcomes (tolerance or various effector mechanisms) occurs when an antigen-bearing DC encounters a T cell of appropriate specificity. The importance of the maturation status of the DC, the subtype of DC involved, modulation by microbial products and the tissue from which the DC was derived are discussed below along with their relevance for responses in the gut.

Alteration in DCs in inflammatory bowel disease

Given that the pathogenesis of inflammatory bowel disease (IBD) is related to dysregulated immune responses to intestinal flora, an examination of the role of DCs as a central mediator demands investigation. We, and others, have noted that DCs in the mucosa of IBD patients show evidence of activation, expressing higher levels of maturation markers such as CD40, CD83 and CD86, than their counterparts in tissue from healthy controls.74., 75., 76. These activated mucosal DCs may represent the ‘tip

Summary

Dendritic cells, and the ways in which they interact with bacteria, regulate gut immunity. Much of what we have learnt about DCs to date has come from the studies on DCs outside the gastrointestinal tract—from the blood or from the more accessible lymphoid tissues. A picture has emerged of a type of cell acting in innate immunity and at the earliest stages of an acquired immune response to shape many aspects of the developing response. DCs can generate both regulatory and effector lymphocytes

Acknowledgements

Work in the authors' laboratory is supported by the Medical Research Council, UK and The Wellcome Trust.

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