Background
The increasing prevalence of food sensitivities has been attributed to changes in gut microenvironment; however, ubiquitous environmental triggers such as inorganic nanoparticles (NPs) used as food additives have not been thoroughly investigated. Objectives: We explored the impact of the NP-structured food-grade silicon dioxide (fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mi>SiO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>) on intestinal immune response involved in oral tolerance (OT) induction and evaluated the consequences of oral chronic exposure to this food-additive using a mouse model of OT to ovalbumin (OVA) and on gluten immunopathology in mice expressing the celiac disease risk gene, HLA-DQ8.
Discussion
Our results suggest that chronic oral exposure to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> blocked oral tolerance induction to OVA, and worsened gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between SiO2SiO2<math><mrow><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> exposure and food sensitivities in humans. https://doi.org/10.1289/EHP12758.
Methods
Viability, proliferation, and cytokine production of mesenteric lymph node (MLN) cells were evaluated after exposure to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mi>SiO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>. C57BL/6J mice and a mouse model of OT to OVA were orally exposed to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mi>SiO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> or vehicle for 60 d. Fecal lipocalin-2 (Lcn-2), anti-OVA IgG, cytokine production, and immune cell populations were analyzed. Nonobese diabetic (NOD) mice expressing HLA-DQ8 (NOD/DQ8), exposed to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mi>SiO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> or vehicle, were immunized with gluten and immunopathology was investigated.
Results
MLN cells exposed to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> presented less proliferative T cells and lower secretion of interleukin 10 (IL-10) and transforming growth factor beta (TGF-βTGF-β<math><mrow><mtext>TGF-</mtext><mi>β</mi></mrow></math>) by T regulatory and CD45+CD45+<math><mrow><mtext>CD</mtext><mrow><msup><mrow><mn>45</mn></mrow><mrow><mo>+</mo></mrow></msup></mrow></mrow></math> CD11b+CD11b+<math><mrow><mtext>CD</mtext><mn>11</mn><mrow><msup><mrow><mi>b</mi></mrow><mrow><mo>+</mo></mrow></msup></mrow></mrow></math> CD103+CD103+<math><mrow><mtext>CD</mtext><mrow><msup><mrow><mn>103</mn></mrow><mrow><mo>+</mo></mrow></msup></mrow></mrow></math> cells compared to control, two factors mediating OT. Mice given fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> exhibited intestinal Lcn-2 level and interferon gamma (IFN-γIFN-γ<math><mrow><mtext>IFN-</mtext><mi>γ</mi></mrow></math>) secretion, showing inflammation and less production of IL-10 and TGF-βTGF-β<math><mrow><mtext>TGF-</mtext><mi>β</mi></mrow></math>. These effects were also observed in OVA-tolerized mice exposed to fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>, in addition to a breakdown of OT and a lower intestinal frequency of T cells. In NOD/DQ8 mice immunized with gluten, the villus-to-crypt ratio was decreased while the CD3+CD3+<math><mrow><mtext>CD</mtext><mrow><msup><mrow><mn>3</mn></mrow><mrow><mo>+</mo></mrow></msup></mrow></mrow></math> intraepithelial lymphocyte counts and the Th1 inflammatory response were aggravated after fg-SiO2fg-SiO2<math><mrow><mi>f</mi><mi>g</mi><mtext>-</mtext><mrow><msub><mrow><mtext>SiO</mtext></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math> treatment.