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Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Lozano-Ojalvo, D. (author), Benede, S. (author), Antunes, C.M. (author), Bavaro, S.L. (author), Bouchaud, G. (author), Costa, A. (author), Denery-Papini, S. (author), Diaz-Perales, A. (author), Garrido-Arandia, M. (author), Gavrovic-Jankulovic, M. (author), Hayen, S. (author), Martinez-Blanco, M. (author), Molina, E. (author), Monaci, L. (author), Pieters, R.H.H. (author), Villemin, C. (author), Wichers, H.J. (author), Wroblewska, B. (author), Willemsen, L.E.M. (author), Roggen, E.L. (author), van Bilsen, J.H.M. (author)

Background: Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the...

article 2019

document

A practical approach to assess inhalation toxicity of metal oxide nanoparticles in vitro

Dankers, A.C.A. (author), Kuper, C.F. (author), Boumeester, A.J. (author), Fabriek, B.O. (author), Kooter, I.M. (author), Gröllers-Mulderij, M. (author), Tromp, P. (author), Nelissen, I. (author), Zondervan-Van Den Beuken, E.K. (author), Vandebriel, R.J. (author)

Exposure of humans to metal oxide nanoparticles (NPs) occurs mainly via air, and inhaled metal oxide NPs may generate inflammation. The aim of this study was to investigate the proinflammatory potential of six metal oxide NPs (CeO2, Mn2O3, CuO, ZnO, Co3O4 and WO3; 27–108 μg ml−1) using human primary 3-dimensional airway epithelium (MucilAir™)...

article 2018

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Characterization of the therapeutic properties of Chinese herbal materials by measuring delayed luminescence and dendritic cell-based immunomodulatory response

Sun, M. (author), Chang, W.T. (author), van Wijk, E. (author), He, M. (author), Koval, S. (author), Lin, M.K. (author), Van Wijk, R. (author), Hankemeier, T. (author), van der Greef, J. (author), Wang, M. (author)

Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of “taste” to all herbs; thus, an herb's “taste” is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These properties guide the practitioner with respect to...

article 2017

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Evaluation of the sensitizing potential of food proteins using two mouse models

Smit, J. (author), Zeeuw-Brouwer, M.L.D. (author), van Roest, M. (author), de Jong, G. (author), van Bilsen, J. (author)

The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food...

article 2016

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The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice

Mariman, R. (author), Kremer, S.H.A. (author), Koning, F. (author), Nagelkerken, L. (author)

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...

article 2014

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Probiotic bacteria and the immune system: mechanistic insights and therapeutic implications

Mariman, R. (author)

This thesis aimed to provide insight into the role of microbiota-host interactions in the regulation of mucosal and systemic immunity in the context of IBD. Regulation of microbiota composition (e.g. by probiotics and prebiotics) offers the possibility to modulate immune responses and contribute to the prevention and treatment of (autoimmune) -...

doctoral thesis 2013

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Respiratory sensitization: Advances in assessing the risk of respiratory inflammation and irritation

Vandebriel, R. (author), Callant Cransveld, C. (author), Crommelin, D. (author), Diamant, Z. (author), Glazenburg, B. (author), Joos, G. (author), Kuper, F. (author), Natsch, A. (author), Nijkamp, F. (author), Noteborn, H. (author), Pieters, R. (author), Roberts, D. (author), Roggen, E. (author), Rorije, E. (author), Seed, M. (author), Sewald, K. (author), van den Heuvel, R. (author), van Engelen, J. (author), Verstraelen, S. (author), van Loveren, H. (author)

Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to...

article 2011

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Late rather than early responses of human dendritic cells highlight selective induction of cytokines, chemokines and growth factors by probiotic bacteria.

Verbeek, R. (author), Bsibsi, M. (author), Plomp, A. (author), van Neerven, R.J. (author), te Biesebeke, R. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

The probiotic properties of commensal bacteria including lactobacilli and bifidobacteria are likely to be determined at least in part by their effects on dendritic cells. Like traditional immune stimulants such as lipopolysaccharides (LPS), probiotic bacteria promote maturation of cultured human dendritic cells (DC) by inducing elevated...

article 2010

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Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: Molecular correlates for Th1/Th2 polarization

van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)

Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...

article 2009

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The bradykinin B2 receptor in the early immune response against Listeria infection

Kaman, W.E. (author), Wolterink, A.F.W.M. (author), Bader, M. (author), Boele, L.C.L. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice) were shown to suffer from increased hepatic...

article 2009

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Activation of toll-like receptors and dendritic cells by a broad range of bacterial molecules

Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)

Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...

article 2009

document

Initiating mechanisms of food allergy: Oral tolerance versus allergic sensitization

van Wijk, F. (author), Knippels, L. (author), TNO Kwaliteit van Leven (author)

Immediately after birth the mucosa of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a large variety of foreign antigens. The immune system of the intestine now has to meet the task of discriminating between pathogens and harmless antigens, such as food proteins...

article 2007

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Tolerization of an established αb-crystallin-reactive T-cell response by intravenous antigen

Verbeek, R. (author), van der Mark, K. (author), Wawrousek, E.F. (author), Plomp, A.C. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire...

article 2007

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Towards understanding molecular modes of probiotic action

Marco, M.L. (author), Pavan, S. (author), Kleerebezem, M. (author), TNO Kwaliteit van Leven (author)

The possibility that certain microorganisms might be beneficial to human health is highlighted by the numerous consumer products containing probiotic bacteria. Probiotics are typically administered in food that, following entry into the gastro-intestinal tract, results in measurable health-promoting effects. Although there is a growing list of...

article 2006

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Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors

Verhaagh, S. (author), de Jong, E. (author), Goudsmit, J. (author), Lecollinet, S. (author), Gillissen, G. (author), de Vries, M. (author), van Leuven, K. (author), Que, I. (author), Ouwehand, K. (author), Mintardjo, R. (author), Weverling, G.J. (author), Radošević, K. (author), Richardson, J. (author), Eloit, M. (author), Lowik, C. (author), Quax, P. (author), Havenga, M. (author), TNO Kwaliteit van Leven (author)

Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here, it is reported that CD46 transgenic mice (MYII...

article 2006

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Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration

Jacobs, J.J.L. (author), Lehé, C.L. (author), Hasegawa, H. (author), Elliott, G.R. (author), Das, P.K. (author), TNO Defensie en Veiligheid (author)

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless,...

article 2006

document

Innate, adaptive and regulatory responses in schistosomiasis: Relationship to allergy

Hartgers, F.C. (author), Smits, H.H. (author), van der Kleij, D. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)

Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune hyporesponsiveness are depicted with emphasis on regulatory...

article 2006

document

Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: Efficient human cell infection and bypass of preexisting adenovirus immunity

Vogels, R. (author), Zuijdgeest, D. (author), van Rijnsoever, R. (author), Hartkoorn, E. (author), Damen, I. (author), de Béthune, M.-P. (author), Kostense, S. (author), Penders, G. (author), Helmus, N. (author), Koudstaal, W. (author), Cecchini, M. (author), Wetterwald, A. (author), Sprangers, M. (author), Lemckert, A. (author), Ophorst, O. (author), Koel, B. (author), van Meerendonk, M. (author), Quax, P. (author), Panitti, L. (author), Grimbergen, J. (author), Bout, A. (author), Goudsmit, J. (author), Havenga, M. (author)

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the...

article 2003

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Rat monocyte-derived dendritic cells function and migrate in the same way as isolated tissue dendritic cells

TNO Preventie en Gezondheid (author), Richters, C.D. (author), Mayen, I. (author), Havenith, C.E.G. (author), Beelen, R.H.J. (author), Kamperdijk, E.W.A. (author)

Dendritic cells (DC) are the most potent antigen-presenting cells and are therefore useful to induce immune responses against tumor cells in patients. DC can be generated in vitro from monocytes using GM-CSF and IL-4, the so-called monocyte-derived DC (MoDC). To achieve antitumor responses, MoDC must be able to migrate to the draining lymph...

article 2002

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Increased adjuvant efficacy in stinulation of antibody responses after macrophage elimination in vivo

Leenaars, P.P.A.M. (author), Savelkoul, H.F.J. (author), Hendriksen, C.F.M. (author), van Rooijen-Claassen, N.E. (author), TNO Preventie en Gezondheid (author)

To investigate whether macrophages influence the efficacy of adjuvants, we locally eliminated lymph node macrophages with dichloromethylene diphosphonate containing liposomes before primary immunization. After macrophage elimination, animals were immunized with a soluble antigen (TNP-KLH; 2,4,6-trinitrophenyl-keyhole limpet haemocyanin) either...

article 1997