The varieties of immunological experience: of pathogens, stress, and dendritic cells.

TitleThe varieties of immunological experience: of pathogens, stress, and dendritic cells.
Publication TypeJournal Article
Year of Publication2015
AuthorsPulendran B
JournalAnnu Rev Immunol
Volume33
Pagination563-606
Date Published02/04/2015
ISSN1545-3278
Abstract

In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.

DOI10.1146/annurev-immunol-020711-075049
Alternate JournalAnnu. Rev. Immunol.
PubMed ID25665078
Grant ListAI100663-02 / AI / NIAID NIH HHS / United States
R37AI48638 / AI / NIAID NIH HHS / United States
R37DK057665 / DK / NIDDK NIH HHS / United States
U19AI057266 / AI / NIAID NIH HHS / United States
U19AI090023 / AI / NIAID NIH HHS / United States
U54AI057157 / AI / NIAID NIH HHS / United States
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