Effects of subtoxic concentrations of TiO2 and ZnO nanoparticles on human lymphocytes, dendritic cells and exosome production

Metal oxide nanoparticles are widely used in the paint and coating industry as well as in cosmetics, but the knowledge of their possible interactions with the immune system is very limited. Our aims were to investigate if commercially available TiO2 and ZnO nanoparticles may affect different human immune cells and their production of exosomes, nano-sized vesicles that have a role in cell to cell communication. We found that the TiO2 or ZnO nanoparticles at concentrations from 1 to 100 μg/mL did not affect the viability of primary human peripheral blood mononuclear cells (PBMC). In contrast, monocyte-derived dendritic cells (MDDC) reacted with a dose dependent increase in cell death and caspase activity to ZnO but not to TiO2 nanoparticles. Non-toxic exposure, 10 μg/mL, to TiO2 and ZnO nanoparticles did not significantly alter the phenotype of MDDC. Interestingly, ZnO but not TiO2 nanoparticles induced a down regulation of FcγRIII (CD16) expression on NK-cells in the PBMC population, suggesting that subtoxic concentrations of ZnO nanoparticles might have an effect on FcγR-mediated immune responses. The phenotype and size of exosomes produced by PBMC or MDDC exposed to the nanoparticles were similar to that of exosomes harvested from control cultures. TiO2 or ZnO nanoparticles could not be detected within or associated to exosomes as analyzed with TEM. We conclude that TiO2 and ZnO nanoparticles differently affect immune cells and that evaluations of nanoparticles should be performed even at subtoxic concentrations on different primary human immune cells when investigating potential effects on immune functions.

► ZnO nanoparticles induce cell death of MDDC but not of PBMC.
► ZnO nanoparticles induce caspase activation and DNA fragmentation in MDDC.
► TiO2 nanoparticles are taken up by MDDC but have no effect on their phenotype.
► ZnO nanoparticles induce a significant reduction of CD16 expression on NK cells.
► ZnO and TiO2 nanoparticles have no effect on exosomes produced by MDDC or PBMC.