Abstract
Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.
Highlights
The immune response to infection is complex, involving multiple effector functions that act in a highly coordinated fashion
The immune response to natural human cytomegalovirus (HCMV) infection is broad and complex. This response is effective at limiting HCMV pathogenesis but is not sufficient to prevent the establishment of lifelong latency, to promote the eradication of latent virus nor completely prevent the risk of reinfection
The ability of HCMV to persist in the face of such an immune response is underpinned by the prodigious immune evasion mechanisms encoded by the virus
Summary
The immune response to infection is complex, involving multiple effector functions that act in a highly coordinated fashion. The immune system can develop a memory of infection making it better able to respond to re-infection—a strategy that underpins the process of vaccination. This memory response is elicited by cell-mediated and humoral immunity. In healthy individuals HCMV infection is controlled by the prodigious immune response generated against it. It is a major health burden in the immunocompromised and immune-immature. A number of immunization strategies have been trialed and have, logically, focused upon harnessing aspects of the adaptive immune response to natural infection with. NK cells for the development of effective vaccines in the future
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