The Role of Trained Immunity in Protection against Infectious Diseases: Epigenetic Reprogramming and Long-term Immune Responses

Abstract

Trained immunity, a concept introduced more than a decade ago, defines the non-specific memory capacity of innate immunity by epigenetic and metabolic reprogramming. It involves features of epigenetic and metabolic reprogramming of innate immune cells that induce long-term functional changes in host defense. This review explores the mechanisms and duration of trained immunity, as well as the therapies related to its potential in infectious diseases. A systematic literature search was conducted across PubMed, Google Scholar, and Web of Science for studies published between 2019 and 2025. Experimental and clinical studies on innate immune memory, epigenetic modifications, and metabolic pathways associated with long-term immune responses were selected as study criteria. The synthesized data was narratively summarized to assess key themes, including molecular mechanisms, sustainability, and translational applications. A total of eight studies were included in this review. The findings revealed that trained immunity is mediated by histone modifications, metabolic changes, and long-term myelopoiesis. Studies also show that immune training has varying durations, with effects lasting from weeks to months. Emerging therapeutic strategies will focus on vaccine enhancement, cancer immunotherapy, and sepsis management. However, challenges remain, including a lack of clinical validation, incomplete mechanistic understanding, and ethical concerns. Trained immunity is a promising approach to immunomodulation between innate and adaptive immunity. Future research should aim to conduct clinical trials, assess safety, and develop precision medicine approaches to efficiently utilize this concept in therapeutic applications.