Abstract
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.
Highlights
The ability of the body of developing immune reactions is strongly influenced by the environment
Even if unable to directly initiate an inflammatory reaction, the exposure to NPs might interfere with the effector functions of monocytes and macrophages, including their activation, their polarization, and their memory
Being the innate immune system the first line of defense of the body, and monocytes and macrophages among the first cells which NPs interact with, assessing the outcomes of such interaction becomes a priority in order to avoid harmful effects that can damage tissues and organs of the body both in the case of NPs for medical use and in the case of occasional or unintentional exposure
Summary
The ability of the body of developing immune reactions is strongly influenced by the environment. Being the innate immune system the first line of defense of the body, and monocytes and macrophages among the first cells which NPs interact with, assessing the outcomes of such interaction becomes a priority in order to avoid harmful effects that can damage tissues and organs of the body (induction of uncontrolled inflammation) both in the case of NPs for medical use and in the case of occasional or unintentional exposure. The second consideration is that, as expected, each individual subject responds differently in quantitative terms (the amount of cytokine produced) and in terms of type of response (enhanced reaction vs decreased response) This behavior most likely depends on the past history of exposure of the donor, i.e., age, vaccinations, diseases, etc. It is important to note that, since the same stimulus is able to prime for decreased or increased responses in different donors, the innate memory seems to be a complete reprograming of the reactivity of cells rather than a stimulus-dependent inhibition or enhancement, a reprogramming that, again, most likely depends on the past “history” of the monocytes of each individual
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