Immunocompetent cell targeting by food-additive titanium dioxide.

Area of Science:

• Immunology
• Nanotoxicology
• Gastroenterology

Background:

• Food-grade titanium dioxide (fgTiO2) is a bio-persistent nanoparticle facing regulatory scrutiny.
• Previously, fgTiO2 was thought to accumulate only in quiescent intestinal pigment cells.

Purpose of the Study:

• To identify immunocompetent cell targets of fgTiO2 in humans.
• To develop a mouse model for assessing human-relevant risks of ingested fgTiO2.

Main Methods:

• Multimodal microscopy with single-particle detection.
• Correlative dosimetry to quantify cellular exposures.
• Proximity extension analyses for 92 protein targets.
• Oral Salmonella challenge in a fgTiO2-fed mouse model.

Main Results:

• fgTiO2 is funneled by microfold cells into immunocompetent LysoMac and LysoDC cells in Peyer's patches.
• No measurable perturbation of cell signaling pathways by fgTiO2 alone was observed.
• Salmonella infection induced cell migration and pro-inflammatory signaling, but fgTiO2 did not augment this response.

Conclusions:

• Immunocompetent cells, not quiescent pigment cells, are the primary in vivo targets for fgTiO2.
• A mouse model successfully recapitulates human fgTiO2 tissue distribution and enables risk assessment.