Innate instruction of adaptive immunity was proposed more than 20 years ago as a mechanism by which long-lived lymphocyte responses are targeted to appropriate antigens. At the time Charles Janeway proposed this theory, most of the innate immune receptors were unknown, and the pivotal role of the dendritic cell in instructing T cell priming was debated. There is now overwhelming evidence that the innate and adaptive branches of the immune system must interact to generate immunity. Much of this work has focused on families of innate immune receptors called pattern recognition receptors (PRRs) on dendritic cells, which translate these inflammatory triggers into productive T cell responses. Nevertheless, we are only beginning to understand how these defence molecules shape the generation of immunity. We review the varied roles of one class of PRRs, the NOD-like receptors (NLRs), in immune responses and propose a new model in which adaptive immunity requires coordinated PRR activation within the dendritic cell.
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