Aging is accompanied by a decline in immune surveillance and immunoreactivity, exposing older people to an increased risk of developing cancer, serious infections and reducing their response to protective vaccines. Trained immunity is a de facto memory capacity of the innate immune system, owing to the reprogramming of hematopoietic stem and progenitor cells (HSPCs) and mature myeloid cells. Induction of trained immunity is associated with increased effector functions of innate immune cells and protects young adult mice against a wide range of infections. Here we demonstrate that the induction of trained immunity in old mice reprograms HSPCs and monocytes with characteristics that are both similar and distinct from their young counterparts. We also report that the induction of trained immunity is a very powerful tool for protecting aged mice from lethal bacterial infections and increasing their response to vaccination. We further show that trained immunity is efficiently induced in primary innate immune cells from older individuals. Taken all together, trained immunity-based therapies represent attractive strategies to treat or prevent infectious diseases in older adults.

Code is available here: https://github.com/mbrochut/TR-lab_RNA-seq_Monocytes_aging https://github.com/mbrochut/TR-lab_RNA-seq_HSPC_aging