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Immunocompetent cell targeting by food-additive titanium dioxide
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Alicja Dabrowska ,
Jack Robertson,
Michelle Miniter,
Sebastian Riedle,
Huw Summers ,
Rachel E. Hewitt ,
Adeeba Fathima,
Alessandra Barreto da Silva ,
Carlos A. P. Bastos,
Stuart Micklethwaite ,
Åsa V. Keita,
Johan D. Söderholm ,
Nicole C. Roy ,
Don Otter,
Ravin Jugdaohsingh,
Pietro Mastroeni,
Andy P. Brown ,
Paul Rees ,
Jonathan J. Powell
Nature Communications, Volume: 16, Start page: 6067
Swansea University Authors:
Huw Summers , Paul Rees
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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DOI (Published version): 10.1038/s41467-025-60248-9
Abstract
Food-grade titanium dioxide (fgTiO2) is a bio-persistent particle under intense regulatory scrutiny. Yet paradoxically, the only known cell reservoirs for fgTiO2 are graveyard intestinal pigment cells which are metabolically and immunologically quiescent. Here we identify immunocompetent cell target...
| Published in: | Nature Communications |
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| ISSN: | 2041-1723 |
| Published: |
Springer Nature
2025
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa69898 |
| Abstract: |
Food-grade titanium dioxide (fgTiO2) is a bio-persistent particle under intense regulatory scrutiny. Yet paradoxically, the only known cell reservoirs for fgTiO2 are graveyard intestinal pigment cells which are metabolically and immunologically quiescent. Here we identify immunocompetent cell targets of fgTiO2 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 fgTiO2-containing diet. Epithelial microfold cells selectively funnel fgTiO2 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 fgTiO2 is revealed despite marked same-cell loading. Interestingly, Salmonella causes the fgTiO2-recipient cells to migrate within the patch and, sporadically, to be identified in the lamina propria, thereby fully recreating the intestinal tissue distribution of fgTiO2 in humans. Immunocompetent cells that accumulate fgTiO2 in vivo are now identified and we demonstrate a mouse model that finally enables human-relevant risk assessments of ingested, bio-persistent (nano)particles. |
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| College: |
Faculty of Science and Engineering |
| Funders: |
The authors acknowledge the UK Medical Research Council (grant number MR/R005699/1, awarded to J.J.P.), the UK Engineering and Physical Sciences Research Council (grant EP/N013506/1, awarded to H.D.S.), the UK Biotechnology and Biological Sciences Research Council (grant number BB/P026818/1, awarded to P.R.) and the Swedish Research Council (Grant No. 2021-02566, awarded to J.D.S. and Å.V.K.). Mouse Study 1 was funded by the Riddet Institute through its Centre of Research Excellence funding (awarded to N.C.R. by the New Zealand government). Additional funding was provided by the Ministry for Science and Innovation contract C11 × 1009 through Nutrigenomics New Zealand, a collaboration between AgResearch, Plant and Food Research, and the University of Auckland (awarded to D.O.). J.W.W. is grateful to Girton College and the University of Cambridge Herchel-Smith Fund for supporting him with post-doctoral Fellowships. S.R. was supported by doctoral scholarships from Massey University. |
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