Induction of Innate Immune Memory by Engineered Nanoparticles: A Hypothesis That May Become True

Innate immune memory is the capacity of cells of the innate immune system, such as monocytes and macrophages, to react differently to an inflammatory or infectious challenge if previously exposed to the same or to another agent. Innate immune memory is a protective mechanism, based on epigenetic reprogramming, that ensures effective protection while limiting side effects of tissue damage, by controlling innate/inflammatory responses to repeated stimulations. Engineered nanoparticles (NPs) are novel challenges for our innate immune system, and their ability to induce inflammatory activation, thereby posing health risks, is currently being investigated with controversial results. Besides their putative direct inflammation-inducing effects, we hypothesize that engineered NPs may induce innate memory based on their capacity to induce epigenetic modulation of gene expression. Preliminary results using non-toxic non-inflammatory gold NPs show that in fact NPs can induce memory by modulating in either positive or negative fashion the inflammatory activation of human monocytes to a subsequent bacterial challenge. The possibility of shaping innate/inflammatory reactivity with NPs could open the way to future novel approaches of preventive and therapeutic immunomodulation.