Abstract
The capacity of engineered nanoparticles to activate cells of the innate immune system, in particular monocytes and macrophages, is considered at the basis of their toxic/inflammatory effects. It is, however, evident that even nanoparticles that do not directly induce inflammatory activation, and are therefore considered as safe, can nevertheless induce epigenetic modifications and affect metabolic pathways in monocytes and macrophages. Since epigenetic and metabolic changes are the main mechanisms of innate memory, we had previously proposed that nanoparticles can induce/modulate innate memory, that is, have the ability of shaping the secondary response to inflammatory challenges. In light of new data, it is now possible to support the original hypothesis and show that different types of nanoparticles can both directly induce innate memory, priming macrophages for a more potent response to subsequent stimuli, and modulate bacteria-induced memory by attenuating the priming-induced enhancement. This evidence raises two important issues. First, in addition to overt toxic/inflammatory effects, we should consider evaluating the capacity to induce innate memory and the related epigenetic and metabolic changes in the immunosafety assessment of nanomaterials, since modulation of innate memory may be at the basis of long-term unwanted immunological effects. The other important consideration is that this capacity of nanomaterials could open a new avenue in immunomodulation and the possibility of using engineered nanomaterials for improving immune responses to vaccines and resistance to infections, and modulate anomalous immune/inflammatory reactions in chronic inflammatory diseases, autoimmunity, and a range of other immune-related pathologies.
Highlights
In the last decades two important research fields have crossed paths: nanotechnology and immunology
Another study on the murine macrophage RAW264.7 cell line showed that exposure to silk, poly(lactic-co-glycolic acid) (PLGA), and silica NP induced some metabolic changes that were independent of the NP type; that is, higher glucose consumption and lactate production, high level of itaconate and succinate, decreased amino acids levels, and ATP decrease over time
The ability of NP to interact with innate immunity could be exploited and, through rational engineering, directed toward an intentional enhancement or suppression of immune reactions to treat a range of disease conditions and in preventive vaccination strategies
Summary
In the last decades two important research fields have crossed paths: nanotechnology and immunology. Human monocytes primed in vitro with LXR agonists and challenged after 5 days with a TLR2 agonist, Pam3Cys, showed an inflammatory activation accompanied by epigenetic reprogramming (increased H3K27ac and H3K4me3 on IL-6 and TNF-α promoters) and metabolic reprogramming (increased lactate production and decreased oxygen consumption) with respect to unprimed cells.
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