Macrophages as programmable integrators of disease tolerance across lifespan.

Clinical outcome may depend as much on the host's ability to preserve tissue function as on its ability to eliminate pathogens. The former reflects disease tolerance, with macrophages emerging as programmable integrators of multicellular tolerance networks. These networks are progressively reconfigured with age, altering the balance between tissue-protective and pathological responses, while mRNA vaccines and modulation of MDA5 signaling may offer clinically translatable means of transiently engaging these pathways.