Chapter 5 : The Regulatory Role of Dendritic Cells in the Innate Immune Response

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Cells of the dendritic cells (DC) lineage are continuously produced; they arise from bone marrow hematopoietic stem cells as myeloid progenitors and seed all organism tissues. Although rare, they are ubiquitously distributed in lymphoid and nonlymphoid tissues; together with macrophages, they recognize pathogens and regulate the inflammatory processes. The responsiveness of mucosal DC populations to inflammatory stimuli, in particular their rapid kinetics of recruitment that surprisingly is equivalent to that of neutrophils, underscores their relevance as antigen sentinels and regulators at the mucosal sites. Indeed, in pathological conditions, such as in Crohn’s disease, a good deal of recent evidence suggests that the failure of a physiological innate immune response could degenerate into an autoimmune response. In the absence of inflammation, innocuous antigens that are continuously encountered in the lungs by DCs induce antigen-specific unresponsiveness. In the lymphoid organs, DCs have the unique opportunity to encounter and present antigens to the rare unprimed antigen-specific T cells. Mannose receptors are believed to be expressed by DCs because internalization and presentation of mannosylated proteins are very efficient in DCs. The movement of the pseudopodia in activated DCs involves actin binding proteins, and it can be blocked by the drug cytochalasin D, which stops the polymerization of actin and inhibits phagocytosis. Natural killer (NK) cells activity is primed during the early phases of an immune response, a few hours after infection. As a matter of fact, physiological immune responses originate from a well-controlled inflammatory process.

Citation: Granucci F, Feau S, Zanoni I, Raimondi G, Pavelka N, Vizzardelli C, Ricciardi-Castagnoli P. 2004. The Regulatory Role of Dendritic Cells in the Innate Immune Response, p 95-110. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch5
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Image of FIGURE 1

Model of conventional and unconventional mechanisms of bacterial uptake.

Citation: Granucci F, Feau S, Zanoni I, Raimondi G, Pavelka N, Vizzardelli C, Ricciardi-Castagnoli P. 2004. The Regulatory Role of Dendritic Cells in the Innate Immune Response, p 95-110. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch5
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Image of FIGURE 2

Two possible pathways of DC-mediated NK cell activation. According to the IL-4 pathway, immature DCs in the presence of IL-4 become competent NK cell activators. This process is bidirectional and requires cell-to-cell contact and soluble factors. According to the IL-2 pathway, early-microbial-activated DCs, IL-2 producers, acquire the ability to stimulate NK cells. This process depends on IL-2 and membrane proteins.

Citation: Granucci F, Feau S, Zanoni I, Raimondi G, Pavelka N, Vizzardelli C, Ricciardi-Castagnoli P. 2004. The Regulatory Role of Dendritic Cells in the Innate Immune Response, p 95-110. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch5
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Image of FIGURE 3

DCs link innate and adaptive immune responses. Following microbial encounter, immature DCs increase the efficiency of antigen processing and presentation and express, with a strictly defined kinetic IL-2. At early time points, DC-derived IL-2 helps to activate NK cells (IL-2 pathway; see Fig. 2 ). At later time points, when DCs have not yet reached the final stage of maturation and still express low levels of costimulatory molecules and peptide-MHC complexes at the cell surface, DC-derived IL-2 cooperates in the activation of T-cell responses (late adaptive response). It cannot be excluded that IL-2 can also act on DCs in an autocrine fashion. CTL, cytotoxic T lymphocyte.

Citation: Granucci F, Feau S, Zanoni I, Raimondi G, Pavelka N, Vizzardelli C, Ricciardi-Castagnoli P. 2004. The Regulatory Role of Dendritic Cells in the Innate Immune Response, p 95-110. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch5
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