Immunocompetent cell targeting by food-additive titanium dioxide

Year: 2025

Type: article

Abstract: ABSTRACT Food-grade titanium dioxide (fgTiO 2 ) is a bio-persistent particle under intense regulatory scrutiny. Paradoxically, meaningful in vivo cellular accumulation has never been demonstrated: the only known cell reservoirs for fgTiO 2 are ‘graveyard’ intestinal pigment cells which are metabolically and immunologically quiescent. Here we identify major new immunocompetent cell targets of fgTiO 2 in humans, most notably in the subepithelial dome region of intestinal Peyer’s patches. Using multimodal microscopy techniques with single-particle detection and per-cell / vesicle image analysis we achieved correlative dosimetry, quantitatively recapitulating human cellular exposures in the terminal ileum of mice fed a fgTiO 2 -containing diet. Epithelial microfold cells selectively funneled fgTiO 2 into LysoMac and LysoDC cells with ensuing accumulation. Notwithstanding, proximity extension analyses for 92 protein targets revealed no measureable perturbation of cell signalling pathways. When chased with oral Δ aroA - Salmonella , pro-inflammatory signalling was confirmed, but no augmentation by fgTiO 2 was revealed despite marked same-cell loading. Interestingly, Salmonella caused the fgTiO 2 -recipient cells to migrate basolaterally in the patch and, sporadically, to the lamina propria, thereby fully recreating the intestinal tissue distribution of fgTiO 2 in humans. Immunocompetent cells that accumulate fgTiO 2 in vivo are now identified and we demonstrate a mouse model that finally enables human-relevant risk assessments of ingested, bio-persistent (nano)particles.

Source: Nature Communications

DOI: 10.1038/s41467-025-60248-9

Institutions: University of Cambridge, AgResearch, Riddet Institute, Massey University, Swansea University, University of Leeds, Linköping University, University of Otago, Auckland University of Technology, Broad Institute

Language: English

Topic: Immunotoxicology and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Vetenskapsrådet, Medical Research Council, Biotechnology and Biological Sciences Research Council

Awards: Biominerals in Health and Disease, Crucial role of intestinal barrier dysfunction in inflammatory bowel disease – identifying novel therapeutic targets, Open access deep learning solutions for imaging flow cytometry, G3936385509

OpenAlex ID: W4412038624