Memory is literally a life-saving property of the immune system of vertebrate organisms against pathogens. Immune memory allows vaccines to prime the immune system so that a fast and efficient immune response is mounted upon subsequent encounter with the corresponding pathogen.

Up till quite recently, immune memory was solely attributed to the adaptive immune system, B and T lymphocytes. However, increasing evidence challenges this central dogma in immunology, with convincing examples of memory-like features in innate immune cell populations, in particular natural killer (NK) cell memory against specific viruses and haptens. Such innate immune memory or trained innate immunity obviously may have an enormous impact on future vaccine design strategies, particularly for pathogens against which traditional vaccination approaches have been unsuccessful. Despite several attempts, different important alphaherpesviruses, e.g. herpes simplex virus (HSV) and equine herpesvirus 1 (EHV1), still lack (effective) vaccines. Since no alphaherpesviruses have been described in rodents, alternative animal models are required to investigate the complex and evolutionary shaped interactions between these pathogens and the (innate) immune system of their natural host, including possible NK cell memory responses.

Recently, using the porcine alphaherpesvirus pseudorabies virus (PRV), we have generated the first controlled evidence of NK cell memory against alphaherpesviruses. In addition, we have recently identified a porcine liver NK cell population (Eomes^high-T-bet^low NK cells) that shows remarkable similarity to human liver NK cells, but is different from mouse liver NK cells as the latter a.o. show a reverse expression pattern of T-box transcription factors (Eomes^low-T-bet^high). Since these liver NK cells are of particular relevance in the context of NK cell memory, our findings on PRV and porcine (liver) NK cells not only provide the first animal model to study NK cell memory against alpha-herpesviruses, but also highlight the pig as a unique model with translational potential to study this fascinating but still largely enigmatic aspect of NK cell biology. Therefore, in the current project, we will mechanistically investigate NK cell memory against alphaherpesviruses in the pig.