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Chapter 3 : Dendritic Cells and Their Tissue Microenvironment during Exposure to Pathogens
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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Myeloid dendritic cells (DCs) are found in all mucosal tissues and sites of pathogen entry, such as the gut and the lung, in particular. Human DCs are easy to isolate from blood. Such blood-derived DCs have been extensively studied as prototype DCs, although it remains unclear whether their functional properties are representative of tissue DCs. The active transcriptional response leads to the acquisition of diverse DC functional phenotypes that orchestrate the appropriate immune response. This chapter deals with the origin, tissue distribution, and common effector functions of myeloid DCs. Common myeloid progenitors (CMPs) in the bone marrow (BM) develop into monoblasts, which are released into the bloodstream as monocytes—a pool of progenitor cells from which tissue DCs and macrophages develop. The skin carries out immune surveillance through a multitude of cutaneous DCs. DCs are particularly abundant in the intestinal mucosa, which interfaces with the external environment, and in which they function as efficient sentinels. Tolerance to tissue antigens is achieved through a combination of thymic and peripheral events eliminating or inactivating potentially dangerous T cells. Many tissue proteins are not expressed at sufficiently high levels in the thymus to induce clonal deletion or tolerance. There is growing evidence that DC plasticity is the result of both endogenous and exogenous signals; in addition, depending on the microenvironment tissue, DCs might be conditioned to acquire very different functional properties leading to immunity or tolerance.