Cellular and Molecular Mechanisms of Innate Memory Responses

There has been an increasing effort to understand the memory responses of a complex interplay among innate, adaptive, and structural cells in peripheral organs and bone marrow. Trained immunity is coined as the de facto memory of innate immune cells and their progenitors. These cells acquire epigenetic modifications and shift their metabolism to equip an imprinted signature to a persistent fast-responsive functional state. Recent studies highlight the contribution of noncoding RNAs and modulation of chromatin structures in establishing this epigenetic readiness for potential immune perturbations. In this review, we discuss recent studies that highlight trained immunity–mediated memory responses emerging intrinsically in innate immune cells and as a complex interplay with other cells at the organ level. Lastly, we survey epigenetic contributors to trained immunity phenotypes—specifically, a recently discovered regulatory circuit coordinating the regulation of a key driver of trained immunity.