Immune Adaptation to Environmental Influence: The Case of NK Cells and HCMV

The immune system of an individual human is determined by heritable traits and a continuous process of adaptation to a broad variety of extrinsic, non-heritable factors such as viruses, bacteria, dietary components and more. Cytomegalovirus (CMV) successfully infects the majority of the human population and establishes latency, thereby exerting a life-long influence on the immune system of its host. CMV has been shown to influence the majority of immune parameters in healthy individuals. Here we focus on adaptive changes induced by CMV in subsets of Natural Killer (NK) cells, changes that question our very definition of adaptive and innate immunity by suggesting that adaptations of immune cells to environmental influences occur across the entire human immune system and not restricted to the classical adaptive branch of the immune system.

TrendsHuman immune systems vary in healthy individuals as a consequence of non-heritable more than heritable influences.Cytomegalovirus (CMV) has emerged as one key factor with a broad influence on the human immune system, impacting the majority of cell populations and serum proteins.Specific populations of natural killer (NK) cells, predominantly expressing the activating receptor NKG2C and the carbohydrate antigen CD57, expand as a consequence of CMV infection and display certain hallmarks of adaptive immune responses (e.g., clonal expansion, functional superiority, long-term persistence).CMV-adapted NK cells are characterized by decreased expression of multiple signaling molecules and transcription factors as well as broad epigenetic modifications.Functionally, CMV-adapted NK cells are superior in performing antibody-dependent cellular cytotoxicity (ADCC), rendering them a potential therapeutic target.