Mapping the diversity of trained immunity against live bacteria: plasticity of macrophage response in homeostasis and disease

Abstract

In the past decade, the existence of long-term consequences of the stimulation of innate immune cells has been recognized, resulting in divergent immune responses to secondary challenges. Trained immunity has redefined our understanding of the innate immune system modulation. Using certain single molecular patterns or vaccine-like formulations, it has been proposed as a promising strategy against inflammatory/infectious insults due to its capacity to generate heterologous cross-protection. However, the phenotype and regulatory mechanisms of innate immune memory against live bacteria have been largely unaddressed. These interactions might be particularly relevant in the context of persistent infections and the maintenance of homeostasis by gut commensals, where the repeated exposure of innate cells to microorganisms may shape the evolving response.