Titanium dioxide nanoparticles temporarily influence the sea urchin immunological state suppressing inflammatory-relate gene transcription and boosting antioxidant metabolic activity

Titanium dioxide nanoparticles (TiO2 NPs) are revolutionizing biomedicine due to their potential application as diagnostic and therapeutic agents. However, the TiO2 NP immune-compatibility remains an open issue, even for ethical reasons. In this work, we investigated the immunomodulatory effects of TiO2 NPs in an emergent proxy to human non-mammalian model for in vitro basic and translational immunology: the sea urchin Paracentrotus lividus. To highlight on the new insights into the evolutionarily conserved intracellular signaling and metabolism path- ways involved in immune-TiO2 NP recognition/interaction we applied a wide-ranging approach, including elec- tron microscopy, biochemistry, transcriptomics and metabolomics. Findings highlight that TiO2 NPs interact with immune cells suppressing the expression of genes encoding for proteins involved in immune response and apop- tosis (e.g. NF-?B, FGFR2, JUN, MAPK14, FAS, VEGFR, Casp8), and boosting the immune cell antioxidant meta- bolicactivity(e.g.pentosephosphate,cysteine-methionine,glycine-serinemetabolismpathways).TiO2 NPuptake was circumscribed to phagosomes/phagolysosomes, depicting harmless vesicular internalization. Our ndings underlined that under TiO2 NP-exposure sea urchin innate immune system is able to control in ammatory signal- ing, excite antioxidant metabolic activity and acquire immunological tolerance, providing a new level of under- standing of the TiO2NP immune-compatibility that could be useful for the development in Nano medicines.