FIG 5.

Administration of stimuli at the (future) site of injury can induce central innate immune memory, peripheral innate immune memory, and/or trained tissue repair. Central innate immune memory is induced by training of bone marrow precursors, resulting in “trained” blood monocytes and neutrophils. Peripheral innate immune memory arises upon training of resident macrophages. By increasing their effector functions, “trained” innate immune cells enhance bacterial clearance. Trained tissue repair is mediated by training of nonimmune cells (e.g., epithelial stem cells, mesenchymal stem cells) and results in enhanced wound closure. As the cells involved often have multiple functions, we hypothesize a contribution of “trained” keratinocytes to host defense by increasing their production in cytokines and antimicrobial defensins. Moreover, “trained” macrophages might contribute to trained tissue repair by an increase in their production of growth factors.