Immunocompetent cell targeting by food-additive titanium dioxide.

Nature communications
Authors
Abstract

Food-grade titanium dioxide (fgTiO) is a bio-persistent particle under intense regulatory scrutiny. Yet paradoxically, the only known cell reservoirs for fgTiO are graveyard intestinal pigment cells which are metabolically and immunologically quiescent. Here we identify immunocompetent cell targets of fgTiO in humans, most notably in the subepithelial dome region of intestinal Peyer's patches. Using multimodal microscopies with single-particle detection and per-cell / vesicle image analysis we achieve correlative dosimetry, quantitatively recapitulating human cellular exposures in the ileum of mice fed a fgTiO-containing diet. Epithelial microfold cells selectively funnel fgTiO into LysoMac and LysoDC cells with ensuing accumulation. Notwithstanding, proximity extension analyses for 92 protein targets reveal no measureable perturbation of cell signalling pathways. When chased with oral ΔaroA-Salmonella, pro-inflammatory signalling is confirmed, but no augmentation by fgTiO is revealed despite marked same-cell loading. Interestingly, Salmonella causes the fgTiO-recipient cells to migrate within the patch and, sporadically, to be identified in the lamina propria, thereby fully recreating the intestinal tissue distribution of fgTiO in humans. Immunocompetent cells that accumulate fgTiO in vivo are now identified and we demonstrate a mouse model that finally enables human-relevant risk assessments of ingested, bio-persistent (nano)particles.

Year of Publication
2025
Journal
Nature communications
Volume
16
Issue
1
Pages
6067
Date Published
07/2025
ISSN
2041-1723
DOI
10.1038/s41467-025-60248-9
PubMed ID
40615368
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