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

• TiO 2 NPs excite sea urchin immune cell adherence and phagocytic activity. • TiO 2 NPs have a suppressive effects on transcripts involved in inflammation. • TiO 2 NPs activate antioxidant defense metabolic pathways. • Immune system rewires metabolism promoting tolerance under TiO 2 NP-exposure. Titanium dioxide nanoparticles (TiO 2 NPs) are revolutionizing biomedicine due to their potential application as diagnostic and therapeutic agents. However, the TiO 2 NP immune-compatibility remains an open issue, even for ethical reasons. In this work, we investigated the immunomodulatory effects of TiO 2 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 pathways involved in immune-TiO 2 NP recognition/interaction we applied a wide-ranging approach, including electron microscopy, biochemistry, transcriptomics and metabolomics. Findings highlight that TiO 2 NPs interact with immune cells suppressing the expression of genes encoding for proteins involved in immune response and apoptosis (e.g. NF-κB, FGFR2, JUN, MAPK14, FAS, VEGFR, Casp8), and boosting the immune cell antioxidant metabolic activity (e.g. pentose phosphate, cysteine-methionine, glycine-serine metabolism pathways). TiO 2 NP uptake was circumscribed to phagosomes/phagolysosomes, depicting harmless vesicular internalization. Our findings underlined that under TiO 2 NP-exposure sea urchin innate immune system is able to control inflammatory signaling, excite antioxidant metabolic activity and acquire immunological tolerance, providing a new level of understanding of the TiO 2 NP immune-compatibility that could be useful for the development in Nano medicines. [ABSTRACT FROM AUTHOR]