About Training and Memory: NK-Cell Adaptation to Viral Infections

Viral infections continuously challenge and shape our immune system. Due to their fine antigen recognition ability, adaptive lymphocytes protect against pathogen reencounter by generating specific immunological memory. Innate cells such as macrophages also adapt to pathogen challenge and mount resistance to reinfection, a phenomenon termed trained immunity. As part of the innate immunity, natural killer (NK) cells can display rapid effector functions and play a crucial role in the control of viral infections, especially by the β-herpesvirus cytomegalovirus (CMV). CMV activates the NK-cell pool by inducing proinflammatory signals, which prime NK cells, paralleling macrophage training. In addition, CMV dramatically shapes the NK-cell repertoire due to its ability to trigger specific NK cell-activating receptors, and enables the expansion and persistence of a specific NK-cell subset displaying adaptive and memory features. In this chapter, we will discuss how different signals during CMV infection contribute to NK-cell training and acquisition of classical memory properties and how these events can impact on reinfection and cross-resistance.