Regulation of the human NK cell compartment by pathogens and vaccines

Natural killer cells constitute a phenotypically diverse population of innate lymphoid cells with a broad functional spectrum. Classically defined as cytotoxic lymphocytes with the capacity to eliminate cells lacking self‐MHC or expressing markers of stress or neoplastic transformation, critical roles for NK cells in immunity to infection in the regulation of immune responses and as vaccine‐induced effector cells have also emerged. A crucial feature of NK cell biology is their capacity to integrate signals from pathogen‐, tumor‐ or stress‐induced innate pathways and from antigen‐specific immune responses. The extent to which innate and acquired immune mediators influence NK cell effector function is influenced by the maturation and differentiation state of the NK cell compartment; moreover, NK cell differentiation is driven in part by exposure to infection. Pathogens can thus mould the NK cell response to maximise their own success and/or minimise the damage they cause. Here, we review recent evidence that pathogen‐ and vaccine‐derived signals influence the differentiation, adaptation and subsequent effector function of human NK cells.