Cell Targeting and Adjuvant Activity of Dietary Titanium Dioxide
Listed in
This article is not in any list yet, why not save it to one of your lists.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 targets for fgTiO 2 are ‘graveyard’ intestinal pigment cells which are metabolically and immunologically quiescent. Here, we identify major new immunocompetent cell reservoirs 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 a mouse model. Epithelial microfold cells specifically funneled fgTiO 2 into LysoMac and LysoDC cells, which co-accumulated attenuated Δ aroA - Salmonella upon sequential oral challenge. By proximity extension analyses, a clear Salmonella effect on pro-inflammatory signalling was confirmed, but no interaction with fgTiO 2 was revealed for 92 protein targets despite marked same-cell accumulation. In contrast, Salmonella caused the fgTiO 2 -recipient cells to migrate towards the follicle margins and, sporadically, to the lamina propria recreating the human intestinal tissue distribution of fgTiO 2 . Physiologically active cell targets that accumulate fgTiO 2 are now identified. fgTiO 2 appears neither a danger signal nor an adjuvant in wild-type genotypes and we demonstrate a mouse model that finally enables human-relevant risk assessments of ingested (nano)particles.
