Activation of dendritic cells: translating innate into adaptive immunity
Introduction
The adaptive immune system, found exclusively in vertebrates, evolved from an ancient innate defence mechanism common to all metazoans. Given this past, it is not surprising that adaptive immunity takes its cues from the innate immune system. Indeed, as postulated by Janeway [1], it is now abundantly clear that innate signalling precedes, and is essential for, the generation of T-cell and B-cell responses. Central to this process are the dendritic cells (DCs), a heterogeneous family of leukocytes that integrate innate information and convey it to lymphocytes. Innate stimulation of DCs can trigger their differentiation into immunogenic antigen-presenting cells (APCs) capable of priming and sustaining the expansion of naı̈ve T cells. In addition, DCs direct T-cell effector differentiation, thus being responsible for ensuring that the specificity of the innate immune system, which distinguishes between many classes of potential pathogens, is translated into an equally specific class of adaptive immune response. This review focuses on our emerging understanding of the mechanisms involved in innate activation of DCs and how they may impact on immunity.
Section snippets
Innate activation of dendritic cells
There are several distinct mechanisms leading to innate DC activation, all of which probably share an evolutionary link to infection [2]. In this review, a distinction is made between pattern recognition pathways, which allow direct or indirect detection of conserved molecular signatures of potential pathogens (the so-called ‘pathogen-associated molecular patterns’, or PAMPs; [1]), and PAMP-independent DC activation in response to self-molecules or alterations in the internal milieu (Figure 1).
Conclusions
Microbial components and inflammatory cytokines have long been known to profoundly affect DC phenotype and function. However, the pathways involved in infection sensing by DCs still remain elusive. Recent advances in our understanding of innate immunity, including the molecular identification of PRRs (e.g. TLRs) and sensors of altered self (e.g. NKG2D), and an increased awareness of the role of inflammatory cytokines in promoting acquired immunity (e.g. IFN-I), have opened the door to molecular
Update
Recent work has demonstrated that uric acid released from dying cells may act as a ‘danger’ signal that promotes cross-priming [46].
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
Acknowledgements
I am grateful to members of the Immunobiology Laboratory, Cancer Research UK, for discussions and critical review of the manuscript.
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