Induction of Innate Memory in Human Monocytes Exposed to Mixtures of Bacterial Agents and Nanoparticles

Abstract

Innate memory; Macrophages; Monocytes

Memoria innata; Macrófagos; Monocitos

Memòria innata; Macròfags; Monòcits

We assessed whether concomitant exposure of human monocytes to bacterial agents and different engineered nanoparticles can affect the induction of protective innate memory, an immune mechanism that affords better resistance to diverse threatening challenges. Monocytes were exposed in vitro to nanoparticles of different chemical nature, shape and size either alone or admixed with LPS, and cell activation was assessed in terms of production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). After return to baseline conditions, cells were re-challenged with LPS and their secondary “memory” response measured. Results show that nanoparticles alone are essentially unable to generate memory, while LPS induced a tolerance memory response (less inflammatory cytokines, equal or increased anti-inflammatory cytokines). LPS-induced tolerance was not significantly affected by the presence of nanoparticles during the memory generation phase, although with substantial donor-to-donor variability. This suggests that, despite the overall lack of significant effects on LPS-induced innate memory, nanoparticles may have donor-specific effects. Thus, future nanosafety assessment and nanotherapeutic strategies will need a personalized approach in order to ensure both the safety and efficacy of nano medical compounds for individual patients.

This work was supported by the EU Commission H2020 projects PANDORA (GA671881) and ENDONANO (GA 812661) (PI, DB), the Italian MIUR InterOmics Flagship projects MEMORAT and MAME (DB, PI), and the Presidential International Fellowship Program (PIFI) of the Chinese Academy of Science (2020VBA0028) (DB). Part of this work was carried out in the context of the JRC Visiting Scientist agreement no. 05/JRC.F.2/2019 (Directorate F—Health, Consumers and Reference Materials, Consumer Products Safety, Nanobiotechnology Lab).