Hematopoietic stem and progenitor cells fine-tunning the “sweet” of trained immunity

Abstract Recent studies have challenged the traditional view of innate immunity as non-specific and transient by demonstrating that innate immune cells can develop immune memory in response to various activating factors, a phenomenon known as trained immunity. This process involves epigenetic modifications, such as changes in chromatin accessibility, and metabolic reprogramming, which can provide protection against unrelated pathogens but may also trigger immune-mediated damage. This review summarizes the current understanding of innate immune memory, with a particular focus on recent findings regarding the training of innate immune cells at the hematopoietic stem and progenitor cell stage. We present observations of trained immunity in innate immune cells, summarize key activating factors and underlying mechanisms, and propose potential host-directed immunotherapeutic strategies and preventive measures based on trained immunity. Our aim is to highlight the biological significance of trained immunity and its potential applications in enhancing long-term immunity, improving vaccine efficacy, and preventing immune-related diseases.