Microparticles and their impact on intestinal immunity.

Microparticles are small (<1 µm), nonbiological particles that are used in many areas of daily life. As food additive they are used as anticaking agents or food colorants. The most common food-derived ingested compounds are aluminium silicate and titanium dioxide (TiO(2)), the latter being a white pigment used in toothpaste or sugar toppings. The increasing abundance of microparticles in the Western diet raises the question of the potential risks associated with gastrointestinal diseases such as Crohn's disease (CD). Accumulation of particles has been shown in cells of Peyer's patches, but it is not clear whether this also has pathological effects. NLRP3 is a member of the intracellular pattern recognition receptor family and it is part of the inflammasome, a multiprotein complex containing caspase-1 which activates the proinflammatory cytokines interleukin (IL)-1β and IL-18. With regard to recent findings identifying small particles such as asbestos and monosodium urate as NLRP3 activators, TiO(2) may be another potential target for inflammasome studies. We found that macrophage-like cells readily take up TiO(2) after 6 h. Incubation of cells with TiO(2) resulted in the assembly of NLRP3 with caspase-1. This inflammasome assembly correlated with secretion of IL-1β. In intestinal epithelial cells, TiO(2) also was found to be ingested. The counting of particles localized intracellularly revealed a dose-dependent increase of TiO(2)-positive cells. This points to the fact that in humans with a leaky intestinal barrier (such as IBD patients), TiO(2) microparticles may be taken up by macrophages and intestinal epithelial cells, may activate the inflammasome and induce IL-1β and IL-18 secretion. This may aggravate inflammation in susceptible individuals.