[Innate immune memory - Trained immunity: Current concepts and clinical implications]

Trained immunity is a phenomenon of growing understanding that redefines the classic view of the innate immune system by demonstrating its ability to develop longlasting functional memory. It is characterized by epigenetic and metabolic reprogramming that enhances the response to new homologous or heterologous stimuli, independently of the adaptive immune system. Known inducers include microbial components, live attenuated vaccines, metabolites, and inflammatory signals, although the magnitude and duration of this memory are not yet fully established. This work reviews the cellular and molecular mechanisms of trained immunity, highlighting its potential benefits in host defense and tumor surveillance, as well as its adverse effects when activation is persistent or dysregulated, leading to chronic inflammatory diseases. It emphasizes the need to identify specific biomarkers and develop accessible techniques to quantify this response, assess its persistence, and understand its interaction with immunoregulatory populations like myeloid-derived suppressor cells (MDSCs). Although trained immunity and MDSCs share common pathophysiological scenarios, such as persistent inflammation and emergency hematopoiesis, data suggest differences in their origins and induction mechanisms. While MDSCs primarily affect neutrophils and monocytes with immunosuppressive functions, trained immunity cells, myeloid and lymphoid, appears to derive from more primitive progenitors, implying a broader reprogramming of the innate immune compartment. Trained immunity holds enormous preventive and therapeutic potential. However, its clinical application requires overcoming technical limitations and gaining a deeper understanding of its induction and regulation mechanisms, its interaction with other immunoregulatory systems, and its pharmacological modulation.