Nanomaterials are increasingly used in various food applications. In particular, nanoparticulate amorphous SiO2 is already contained, e.g., in spices. Since intestinal dendritic cells (DC) could be critical targets for ingested particles, we compared the in vitro effects of amorphous silica nanoparticles with fine crystalline silica, and micron-sized with nano-sized TiO2 particles on DC. TiO2- and SiO2-nanoparticles, as well as crystalline silica led to an upregulation of MHC-II, CD80, and CD86 on DC. Furthermore, these particles activated the inflammasome, leading to significant IL-1β-secretion in wild-type (WT) but not Caspase-1- or NLRP3-deficient mice. Silica nanoparticles and crystalline silica induced apoptosis, while TiO2 nanoparticles led to enhanced production of reactive oxygen species (ROS). Since amorphous silica and TiO2 nanoparticles had strong effects on the activation-status of DC, we suggest that nanoparticles, used as food additives, should be intensively studied in vitro and in vivo, to ensure their safety for the consumer.

Background: Dendritic cell (DC) vaccines can induce antitumor immune responses in patients with malignant diseases, while the most suitable DC culture conditions have not been established yet. In this study we compared monocyte derived human DC from conventional cultures containing GM-CSF and IL-4/TNF-α (IL-4/TNF-DC) with DC generated by the novel protocol using GM-CSF and IFN-α (IFN-DC).

The toxic environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent immunomodulatory chemical. TCDD activates the aryl hydrocarbon receptor (AhR) and suppresses peripheral humoral and cellular adaptive immune responses. Though the major route of uptake is via food, little is known until now on the immunotoxic effects of TCDD on the gut-associated lymphoid tissue. We show here that AhR is strongly expressed along the small intestine, especially in intestinal epithelial cells (IEC). The AhR marker gene cyp1a1 is induced in IEC by oral TCDD exposure. We asked how TCDD affects oral tolerance, a unique function of mucosal immunity. C57BL/6 mice were injected with 10 μg/kg body weight TCDD and fed with ovalbumin (OVA) in a high-dose tolerization protocol. Mice were immunized and boosted with OVA on days 12, 23, and 55 after tolerization. Five of 14, 6 of 15, and 13 of 14 TCDD-treated mice generated OVA-specific immunoglobulin (Ig)G1 antibodies after the first, second, and third immunization with OVA, respectively. Only one mouse harbored anti-OVA IgG1 antibodies in the control group even after the third immunization with OVA. OVA-specific IgA in fecal samples of tolerized and TCDD-exposed mice could be detected at the levels of nontolerized mice, whereas completely absent in tolerant control mice. Correlated to this, we found in TCDD-treated mice an increase in interleukin-6 producing CD103+ dendritic cells (DC) present in the gut-draining mesenteric lymph nodes (MLN) and a small increase in the frequency of Th17 cells. Neither the frequencies nor the absolute numbers of immune cells in the lamina propria (LP) or in intraepithelial lymphocytes were changed by TCDD treatment. Our data not only have implications for food allergies in settings of environmental exposure but also raise concerns regarding the harmlessness of overdosing potential AhR agonist in food, which needs to be studied further.

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ObjectiveIntravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Clinical trials of IVIG for multiple sclerosis, using diverse dose regimens, yielded controversial results. The aim of this study is to dissect IVIG effector mechanisms on demyelination in an ex vivo model of the central nervous system (CNS)‐immune interface.MethodsUsing organotypic cerebellar slice cultures (OSC) from transgenic mice expressing green fluorescent protein (GFP) in oligodendrocytes/myelin, we induced extensive immune‐mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement. Protective IVIG effects were assessed by live imaging of GFP expression, confocal microscopy, immunohistochemistry, gene expression analysis and flow cytometry.Results IVIG protected OSC from demyelination in a dose‐dependent manner, which was at least partly attributed to interference with complement‐mediated oligodendroglia damage, while binding of the anti‐MOG antibody was not prevented. Staining with anti‐CD68 antibodies and flow cytometry confirmed that IVIG prevented microglia activation and oligodendrocyte death, respectively. Equimolar IVIG‐derived Fab fragments or monoclonal IgG did not protect OSC, while Fc fragments derived from a polyclonal mixture of human IgG were at least as potent as intact IVIG.InterpretationBoth intact IVIG and Fc fragments exert a dose‐dependent protective effect on antibody‐mediated CNS demyelination and microglia activation by interfering with the complement cascade and, presumably, interacting with local immune cells. Although this experimental model lacks blood–brain barrier and peripheral immune components, our findings warrant further studies on optimal dose finding and alternative modes of application to enhance local IVIG concentrations at the site of tissue damage.