Universal Immune Learning Ability in Immune and Non-Immune Cells (A Review)

In response to infections, all jawed vertebrate organisms have evolved complex defense systems in which long-term immune memory of previous infections plays a central role. This memory allows the cells of the immune system to recognize pathogens and protect the organism by developing a stronger immune response in case of repeated infections with the same pathogen. Until recently, the long-term immune memory was attributed solely to the adaptive immune system. However, in the last decade, the protective role of innate immune cells has become increasingly apparent. It has been discovered that, in addition to their well-known role in short-term and nonspecific defense, these cells can also acquire a form of long-term memory, enabling them to mount an immune response to unrelated pathogens (heterologous protection), which is enhanced by repeated stimulation. This long-term nonspecific innate immune memory has been termed “trained immunity.” Its occurrence is associated with intensive metabolic rearrangements and epigenetic modifications of innate immune cells. In light of the growing threat of unforeseen epidemics, there is increasing hope that the possibility of creating nonspecific universal vaccines may be linked to the innate immune system. Recently, the capacity for trained immunity has been identified in tissue-resident immune cells. Moreover, the immune memory in non-immune cells, such as fibroblasts, stromal cells, and epithelial stem cells, has also been revealed. This ability has been termed “enhanced trained immunity” or “inflammatory memory.” The significance of tissue-specific induction of trained innate immunity is not yet fully understood, but it may play an important role in local defense against infections, as well as in inflammatory diseases and cancer.