Innate immune memory: a paradigm shift in understanding host defense

Abstract

S the discovery of the clonal selection theory and the description of antigen recognition and presentation, immunologists have traditionally divided immune responses into innate and adaptive categories. The cells of the innate immune system, such as granulocytes, monocytes, macrophages or innate lymphoid cells (ILCs), including natural killer (NK) cells, are activated within minutes of an infection, and they are able to fight a broad range of pathogens efficiently. However, the consensus until recently was that they mount nonspecific responses and they are not able to confer immunological memory on their own. In contrast, the adaptive T cell– or B cell–dependent immune responses are antigen specific1 and they often provide lifelong protection against re-infection2. The dogma that innate immunity is nonspecific has been challenged by the discovery of pattern-recognition receptors, which are responsible for the semi-specific recognition of pathogen-associated molecular patterns from different classes of microorganisms. In turn, this activates the production of proinflammatory mediators, phagocytosis and killing of pathogens3. In addition, the activation of innate immune responses has an essential role in stimulation of the acquired immune system4. An increasing body of evidence suggests that innate immunity can also display adaptive characteristics, a de facto innate immune memory5,6 (Fig. 1). The key concept discussed at the Wellcome Trust Meeting on Innate Immune Memory held in Hinxton, Cambridge, 18–20 March 2015 was that the innate immune system can have memory, which could lead to a paradigm shift away from the view that it is simply an immediate mediator of host resistance and inflammation. The memory characteristics would involve a priming event whereby upon first exposure, cells of the innate immune system would be altered such that upon re-exposure to identical or heterologous stimuli, they would display a heightened response and boost host defense. Evidence was presented, possible mechanisms were discussed, and consequences for the development of vaccines or anti-inflammatory therapeutics were explored.

DOI: 10.1038/ni.3178

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@article{Netea2015InnateIM, title={Innate immune memory: a paradigm shift in understanding host defense}, author={Mihai G. Netea and Eicke Latz and Kingston H G Mills and Luke A. O'Neill}, journal={Nature Immunology}, year={2015}, volume={16}, pages={675-679} }