Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Intestinal stem-cell organoids as experimental models to investigate feed efficiency
Ellen, E.D. ; Taverne, N. ; Taverne-Thiele, J.J. ; Madsen, O. ; Woelders, H. ; Bergsma, R. ; Knol, Egbert F. ; Kar, S.K. ; Haas, Y. de; Groenen, M. ; Wells, J.M. - \ 2018
In: Book of Abstracts of the 69th Annual Meeting of the European Federation of Animal Science. - Wageningen Academic Publishers (Book of Abstracts ) - ISBN 9789086863235 - p. 478 - 478.
Structure dependent-immunomodulation by sugar beet arabinans via a SYK tyrosine kinase-dependent signaling pathway
Meijerink, Marjolein ; Rösch, Christiane ; Taverne, Nico ; Venema, Koen ; Gruppen, Harry ; Schols, Henk A. ; Wells, Jerry M. - \ 2018
Frontiers in Immunology 9 (2018)OCT. - ISSN 1664-3224
Arabinans - C-Type lectin receptors - Dietary fiber - Immunomodulation - Pectin - Structure-function relationship

There is much interest in the immunomodulatory properties of dietary fibers but their activity may be influenced by contamination with microbial-Associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS) and lipoteichoic acids, which are difficult to remove completely from biological samples. Bone marrow-derived dendritic cells (BMDCs) from TLR2x4 double-KO mice were shown to be a reliable approach to analyse the immunomodulatory properties of a diverse range of dietary fibers, by avoiding immune cell activation due to contaminating MAMPs. Several of the 44 tested dietary fiber preparations induced cytokine responses in BMDCs from TLR2x4 double-KO mice. The particulate fractions of linear arabinan (LA) and branched arabinan (BA) from sugar beet pectin were shown to be strongly immune stimulatory with LA being more immune stimulatory than BA. Enzymatic debranching of BA increased its immune stimulatory activity, possibly due to increased particle formation by the alignment of debranched linear arabinan. Mechanistic studies showed that the immunostimulatory activity of LA and BA was independent of the Dectin-1 recognition but Syk kinase-dependent.

Optimized procedures for generating an enhanced, near physiological 2D culture system from porcine intestinal organoids
Hee, B. van der; Loonen, L.M.P. ; Taverne, N. ; Taverne-Thiele, J.J. ; Smidt, H. ; Wells, J.M. - \ 2018
Stem Cell Research 28 (2018). - ISSN 1873-5061 - p. 165 - 171.
Epithelium - Intestinal - Monolayer - Organoids - Porcine
An important practical limitation of the three-dimensional geometry of stem-cell derived intestinal organoids is that it prevents easy access to the apical epithelium for testing food components, microorganisms, bioactive and toxic compounds. To this end, we here report on a new robust method for generating confluent intestinal cell monolayers from single-cell suspensions of enzymatically-dissociated porcine organoids using modified culture conditions. With this method, cell seeding densities can be standardised, overcoming problems with methods based on mechanical dissociation of organoids. Confluent monolayers formed tight junctions with high transepithelial electrical resistance in three days and could be used in experiments for up to two weeks. Multilineage differentiation of ileal stem cells was demonstrated by immunohistochemistry and RT-qPCR of cell-specific transcripts, also unequivocally confirming the controversial existence of Paneth-like cells in the porcine small intestine. The method described here is useful to standardize primary epithelial monolayer formation from intestinal organoids and allows rapid and robust studies of intestinal physiology.
Dietary protein sources differentially affect microbiota, mTOR activity and transcription of mTOR signaling pathways in the small intestine
Kar, Soumya K. ; Jansman, Alfons J.M. ; Benis, Nirupama ; Ramiro-Garcia, Javier ; Schokker, Dirkjan ; Kruijt, Leo ; Stolte, Ellen H. ; Taverne-Thiele, Johanna J. ; Smits, Mari A. ; Wells, Jerry M. - \ 2017
PLoS ONE 12 (2017)11. - ISSN 1932-6203
Dietary protein sources can have profound effects on host-microbe interactions in the gut that are critically important for immune resilience. However more knowledge is needed to assess the impact of different protein sources on gut and animal health. Thirty-six wildtype male C57BL/6J mice of 35 d age (n = 6/group; mean ± SEM body weight 21.9 ± 0.25 g) were randomly assigned to groups fed for four weeks with semi synthetic diets prepared with one of the following protein sources containing (300 g/kg as fed basis): soybean meal (SBM), casein, partially delactosed whey powder, spray dried plasma protein, wheat gluten meal and yellow meal worm. At the end of the experiment, mice were sacrificed to collect ileal tissue to acquire gene expression data, and mammalian (mechanistic) target of rapamycin (mTOR) activity, ileal digesta to study changes in microbiota and serum to measure cytokines and chemokines. By genome-wide transcriptome analysis, we identified fourteen high level regulatory genes that are strongly affected in SBM-fed mice compared to the other experimental groups. They mostly related to the mTOR pathway. In addition, an increased (P < 0.05) concentration of granulocyte colony-stimulating factor was observed in serum of SBM-fed mice compared to other dietary groups. Moreover, by 16S rRNA sequencing, we observed that SBM-fed mice had higher (P < 0.05) abundances of Bacteroidales family S24-7, compared to the other dietary groups. We showed that measurements of genome-wide expression and microbiota composition in the mouse ileum reveal divergent responses to diets containing different protein sources, in particular for a diet based on SBM.
Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles
Velikova, Nadya ; Mas, Nuria ; Miguel-Romero, Laura ; Polo, Lorena ; Stolte, Ellen ; Zaccaria, Edoardo ; Cao, Rui ; Taverne, Nico ; Murguía, José Ramón ; Martinez-Manez, Ramon ; Marina, Alberto ; Wells, Jerry - \ 2017
Nanomedicine: Nanotechnology, Biology, and Medicine 13 (2017)2. - ISSN 1549-9634 - p. 569 - 581.
Drug delivery - Gram negative - Multi-drug resistance - Nanotechnology - Two-component systems
Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr−) permeability barrier for the HKAIs. The observed bactericidal activity against Gr− bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr− and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria.
Effects of in vitro fermentation of barley β-glucan and sugar beet pectin using human fecal inocula on cytokine expression by dendritic cells
Rosch, Christiane ; Taverne, Nico ; Venema, Koen ; Gruppen, Harry ; Wells, Jerry M. ; Schols, Henk A. - \ 2017
Molecular Nutrition & Food Research 61 (2017)1. - ISSN 1613-4125
Batch fermentation - Dendritic cells - Digesta - Human fecal inocula - Immunomodulation

Scope: This study simulates the fermentation process of barley β-glucan and sugar beet pectin in the human colon and monitors the degradation products formed. Additionally, immune effects of the degradation products were investigated. Methods and results: Immunostimulatory activity of fermentation digesta was investigated using bone marrow derived dendritic cells (BMDCs) from toll-like receptor 2/4 (TLR2/4) knockout mice, which were unresponsive to microbe-associated molecular patterns. Cytokine responses were elicited to dietary fibers and not to the SCFA and microbiota. The fermentation digesta were analyzed for their SCFA profiles and glycan metabolites over time. During fermentation the amount of insoluble precipitating fibers increased and induced as well as soluble molecules of lower molecular mass greater amounts of cytokines in BMDCs than the parental fiber. Additionally, high amounts of cytokines can be attributed to soluble galactose-rich beet pectin molecules. Conclusions: The fermentation of the two fibers led to fiber-specific amounts of SCFA, glycosidic metabolites, and different immunomodulatory properties. BMDC from TLR2/4 knockout mice did not respond to the digest microbiota and SCFA, making it a useful approach to study temporal effects of fermentation on the immunomodulatory effects of fibers.

Modelling concentrations of antimicrobial drugs : Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals
Taverne, Femke J. ; Geijlswijk, Ingeborg M. van; Heederik, Dick J.J. ; Wagenaar, Jaap A. ; Mouton, Johan W. - \ 2016
BMC Veterinary Research 12 (2016)1. - ISSN 1746-6148
Allometric scaling - Antimicrobials - Cephalosporins - Companion animals - Food-producing animals - Mathematical models - Pharmacokinetics

Background: To optimize antimicrobial dosing in different animal species, pharmacokinetic information is necessary. Due to the plethora of cephalosporin antimicrobials and animal species in which they are used, assessment of literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal pharmacokinetics in all species is unfeasible. In this study we aimed to describe pharmacokinetic data of cephalosporins by reviewing the available literature for food producing and companion animal species. We assessed the accuracy of interspecies extrapolation using allometric scaling techniques to determine pharmacokinetic characteristics of cephalosporins in animal species for which species/humans not included in the allometric modelling. Results: In general, excretion of cephalosporins takes place mainly through renal mechanisms in the unchanged form and volume of distribution is limited in all animal species. Differences in plasma protein binding capacity and elimination half-life are observed but available information was limited. Using allometric scaling, correlations between body weight (BW) and volume of distribution (Vd) and clearance (Cl) were R 2 > 0.97 and R 2 > 0.95 respectively for ceftazidime, ceftiofur, cefquinome and cefepime but not ceftriaxone. The allometric exponent ranged from 0.80 to 1.31 for Vd and 0.83 to 1.24 for Cl. Correlations on half-life ranged from R2 0.07-0.655 (literature) and R2 0.102-0.876 (calculated). Conclusions: Allometric scaling can be applied for interspecies extrapolation of cephalosporin pharmacokinetic parameters Vd and Cl, but not elimination half-life. We hypothesize that the accuracy could be improved by using more refined scaling techniques.

Immunomodulatory properties of oat and barley β-glucan populations on bone marrow derived dendritic cells
Rosch, Christiane ; Meijerink, Marjolein ; Delahaije, Roy J.B.M. ; Taverne, Nico ; Gruppen, Harry ; Wells, Jerry M. ; Schols, Henk A. - \ 2016
Journal of Functional Foods 26 (2016). - ISSN 1756-4646 - p. 279 - 289.
Dendritic cells - Homogenisation - Immunomodulation - Particulate - Solubility

Specific structures of oat and barley β(1,3)(1,4)-glucans induced different in vitro immunomodulatory effects in bone marrow derived dendritic cells (BMDC) from TLR2/4 knock out mice. All barley β-glucan fractions induced larger amounts of cytokines in BMDCs than their oat equivalents. The particulate fractions of both glucans induced high amounts of cytokines, especially after sample homogenisation. The small particulate barley β-glucans induced more cytokines than the equivalent oat fraction, hence there are more features influencing the immunomodulatory properties of β-glucans than only the particle size. The soluble glucan fraction and heated suspension induced only low amounts of cytokines, but were different for the two β-glucans, indicating that molecular specificity matters for immunomodulation. Immunomodulatory activity is influenced by the insolubility of β-glucans, to which characteristics as particle size, granule conformation and particulate homogeneity are related. Consequently, sample preparation influences the immunomodulatory activity of β-glucans.

Strain-specific features of extracellular polysaccharides and their impact on Lactobacillus plantarum-host interactions
Lee, I.C. ; Caggianiello, Graziano ; Swam, Iris I. van; Taverne, Nico ; Meijerink, Marjolein ; Bron, Peter A. ; Spano, Giuseppe ; Kleerebezem, Michiel - \ 2016
Applied and Environmental Microbiology 82 (2016)13. - ISSN 0099-2240 - p. 3959 - 3970.

Lactobacilli are found in diverse environments and are widely applied as probiotic, health-promoting food supplements. Polysaccharides are ubiquitously present on the cell surface of lactobacilli and are considered to contribute to the species- and strainspecific probiotic effects that are typically observed. Two Lactobacillus plantarum strains, SF2A35B and Lp90, have an obvious ropy phenotype, implying high extracellular polysaccharide (EPS) production levels. In this work, we set out to identify the genes involved in EPS production in these L. plantarum strains and to demonstrate their role in EPS production by gene deletion analysis. A model L. plantarum strain, WCFS1, and its previously constructed derivative that produced reduced levels of EPS were included as reference strains. The constructed EPS-reduced derivatives were analyzed for the abundance and sugar compositions of their EPS, revealing cps2-like gene clusters in SF2A35B and Lp90 responsible for major EPS production. Moreover, these mutant strains were tested for phenotypic characteristics that are of relevance for their capacity to interact with the host epithelium in the intestinal tract, including bacterial surface properties as well as survival under the stress conditions encountered in the gastrointestinal tract (acid and bile stress). In addition, the Toll-like receptor 2 (TLR2) signaling and immunomodulatory capacities of the EPS-negative derivatives and their respective wild-type strains were compared, revealing strain-specific impacts of EPS on the immunomodulatory properties. Taken together, these experiments illustrate the importance of EPS in L. plantarum strains as a strain-specific determinant in host interaction.

Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses
Rossi, Oriana ; Berkel, Lisette A. Van; Chain, Florian ; Tanweer Khan, M. ; Taverne, Nico ; Sokol, Harry ; Duncan, Sylvia H. ; Flint, Harry J. ; Harmsen, Hermie J.M. ; Langella, Philippe ; Samsom, Janneke N. ; Wells, J.M. - \ 2016
Scientific Reports 6 (2016). - ISSN 2045-2322 - 12 p.

Faecalibacterium prausnitzii strain A2-165 was previously reported to have anti-inflammatory properties and prevent colitis in a TNBS model. We compared the immunomodulatory properties of strain A2-165 to four different F. prausnitzii isolates and eight abundant intestinal commensals using human dendritic cells (DCs) and mouse BMDCs in vitro. Principal component analysis revealed that the cytokine response to F. prausnitzii A2-165 is distinct from the other strains in eliciting high amounts of IL-10 secretion. The mouse DNBS model of relapsing IBD was used to compare the protective effects of F. prausnitzii A2-165 and Clostridium hathewayi, a low secretor of IL-10, on the Th1-driven inflammatory response to DNBS; attenuation of disease parameters was only observed with F. prausnitzii. In an in vivo mouse model of nasal tolerance to ovalbumin, F. prausnitzii A2-165 enhanced ovalbumin-specific T cell proliferation and reduced the proportion of IFN-Yγ+ T cells in CLNs. Similarly, in vitro F. prausnitzii A2-165 stimulated BMDCs increased ovalbumin-specific T cell proliferation and reduced the number of IFN-γ+ T cells. These mechanisms may contribute to the anti-inflammatory effects of F. prausnitzii in colitis and support the notion that this abundant bacterium might contribute to immune homeostasis in the intestine via its anti-inflammatory properties.

The agr Inhibitors Solonamide B and Analogues Alter Immune Responses to Staphylococccus aureus but Do Not Exhibit Adverse Effects on Immune Cell Functions
Baldry, Mara ; Kitir, Betöl ; Frøkir, Hanne ; Christensen, S.B. ; Taverne, Nico ; Meijerink, Marjolein ; Franzyk, Henrik ; Olsen, C.A. ; Wells, J.M. ; Ingmer, Hanne - \ 2016
PLoS ONE 11 (2016)1. - ISSN 1932-6203 - 17 p.

Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-Associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surfaceexpressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of ?-hemolysin and phenol-solublemodulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential tomodulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization.

Influence of applying different units of measurement on reporting antimicrobial consumption data for pig farms
Taverne, F.J. ; Jacobs, J.H. ; Heederik, D.J.J. ; Mouton, J.W. ; Wagenaar, J.A. ; Geijlswijk, I.M. van - \ 2015
BMC Veterinary Research 11 (2015). - ISSN 1746-6148 - 9 p.
Antimicrobial consumption monitoring - Daily dosages - International - Livestock - Methodology - Veterinary medicine

Background: Antimicrobial use in livestock is one of the factors contributing to selection and spread of resistant microorganisms in the environment. National veterinary antimicrobial consumption monitoring programs are therefore in place in a number of countries in the European Union. However, due to differences in methodology, results on veterinary antimicrobial consumption from these national monitoring programs cannot be compared internationally. International comparison is highly needed to establish regulations on veterinary antimicrobial use and reducing antimicrobial resistance. The aim of this study was to assess differences in the outcomes on veterinary antimicrobial consumption by applying three different sets of nationally established animal defined daily dosages to the same antimicrobial drug delivery dataset of Dutch pigs in 2012. Methods: Delivery information for the complete Dutch pig sector for the year 2012 reported to the Netherlands Veterinary Medicines Authority (SDa) was analysed with three differently and nationally established animal defined daily dosages from the Netherlands and Denmark: the Defined Daily Dosage AnimalNL (DDDANL), the Animal Daily DosageDK (ADDDK) and Defined Animal Daily DosageDK (DADDDK). For each applied Dutch product equivalent, Danish products were identified based on authorization for pigs, active substance (including form), administration route, concentration and dosage regimen. Results: Consumption in number of ADDDK/Y was lower than in number of DDDANL/Y for sows/piglets and finisher pigs, with proportions of 83.3 % and 98.3 %. Use in number of DADDDK/Y was even lower, 79.7 % for sows/piglets and 88.1 % for finisher pigs compared to number of DDDANL/Y. At therapeutic group level proportions of number of DADDDK/Y to number of DDDANL/Y were 63.6-150.4 % (sows/piglets) and 55.6-171.0 % (finisher pigs). Proportions were > 100 % for the polymyxines (sows/piglets 150.4 % and finisher pigs 149.9 %) and the macrolides/lincosamides (finisher pigs 171.0 %). Conclusions: Differences between nationally established animal defined daily dosages caused by different correction factors for long-acting products and national differences in authorized dosages, have a substantial influence on the results of antimicrobial consumption in pigs. To enable international comparison of veterinary antimicrobial consumption data, harmonized units of measurement, animal weights and animal (sub) categories are needed.

Recombinant invasive Lactococcus lactis can transfer DNA vaccines either directly to dendritic cells or across an epithelial cell monolayer
Azevedo, Marcela de; Meijerink, Marjolein ; Taverne, Nico ; Pereira, Vanessa Bastos ; LeBlanc, Jean Guy ; Azevedo, Vasco ; Miyoshi, Anderson ; Langella, Philippe ; Wells, J.M. ; Chatel, Jean Marc - \ 2015
Vaccine 33 (2015)38. - ISSN 0264-410X - p. 4807 - 4812.
Dendritic cells - DNA delivery - Internalization - Lactococcus lactis - Listeria monocytogenes - Mutated internalin A - β-lactoglobulin

Lactococcus lactis (L. lactis), a generally regarded as safe (GRAS) bacterium has recently been investigated as a mucosal delivery vehicle for DNA vaccines. Because of its GRAS status, L. lactis represents an attractive alternative to attenuated pathogens. Previous studies showed that eukaryotic expression plasmids could be delivered into intestinal epithelial cells (IECs) by L. lactis, or recombinant invasive strains of L. lactis, leading to heterologous protein expression. Although expression of antigens in IECs might lead to vaccine responses, it would be of interest to know whether uptake of L. lactis DNA vaccines by dendritic cells (DCs) could lead to antigen expression as they are unique in their ability to induce antigen-specific T cell responses. To test this, we incubated mouse bone marrow-derived DCs (BMDCs) with invasive L. lactis strains expressing either Staphylococcus aureus Fibronectin Binding Protein A (LL-FnBPA+), or Listeria monocytogenes mutated Internalin A (LL-mInlA+), both strains carrying a plasmid DNA vaccine (pValac) encoding for the cow milk allergen β-lactoglobulin (BLG). We demonstrated that they can transfect BMDCs, inducing the secretion of the pro-inflammatory cytokine IL-12. We also measured the capacity of strains to invade a polarized monolayer of IECs, mimicking the situation encountered in the gastrointestinal tract. Gentamycin survival assay in these cells showed that LL-mInlA+ is 100 times more invasive than L. lactis. The cross-talk between differentiated IECs, BMDCs and bacteria was also evaluated using an in vitro transwell co-culture model. Co-incubation of strains in this model showed that DCs incubated with LL-mInlA+ containing pValac:BLG could express significant levels of BLG. These results suggest that DCs could sample bacteria containing the DNA vaccine across the epithelial barrier and express the antigen.

Immune-relevant thrombocytes of common carp undergo parasite-induced nitric oxide-mediated apoptosis
Fink, I.R. ; Ribeiro, C.M.S. ; Forlenza, M. ; Taverne-Thiele, J.J. ; Rombout, J.H.W.M. ; Savelkoul, H.F.J. ; Wiegertjes, G. - \ 2015
Developmental and Comparative Immunology 50 (2015)2. - ISSN 0145-305X - p. 146 - 154.
lymphocyte maturation factor - cyprinus-carpio - expression analysis - human platelets - functional-characterization - monoclonal-antibodies - cell-differentiation - teleost fish - genes - l.
Common carp thrombocytes account for 30–40% of peripheral blood leukocytes and are abundant in the healthy animals' spleen, the thrombopoietic organ. We show that, ex vivo, thrombocytes from healthy carp express a large number of immune-relevant genes, among which several cytokines and Toll-like receptors, clearly pointing at immune functions of carp thrombocytes. Few studies have described the role of fish thrombocytes during infection. Carp are natural host to two different but related protozoan parasites, Trypanoplasma borreli and Trypanosoma carassii, which reside in the blood and tissue fluids. We used the two parasites to undertake controlled studies on the role of fish thrombocytes during these infections. In vivo, but only during infection with T. borreli, thrombocytes were massively depleted from the blood and spleen leading to severe thrombocytopenia. Ex vivo, addition of nitric oxide induced a clear and rapid apoptosis of thrombocytes from healthy carp, supporting a role for nitric oxide-mediated control of immune-relevant thrombocytes during infection with T. borreli. The potential advantage for parasites to selectively deplete the host of thrombocytes via nitric oxide-induced apoptosis is discussed.
Paradoxale modernisering : Ede, 1945-1995: groot geworden, herkenbaar gebleven
Bloembergen-Lukkes, J.R. - \ 2014
Wageningen University. Promotor(en): Pim Kooij, co-promotor(en): Anton Schuurman. - Wageningen : Wageningen University - ISBN 9789462571433 - 365
geschiedenis - modernisering - politiek - economie - demografie - cultuur - onderwijs - migratie - ruimtelijke ordening - sociologie van vrijetijdsbesteding - lokale geschiedenis - veluwe - nederland - history - modernization - politics - economics - demography - culture - education - migration - physical planning - sociology of leisure - local history - netherlands

Summary

Paradoxical Modernization

Ede, 1945-1995: Grew big, remained recognizable

After the Second World War, like many other municipalities in the Netherlands and elsewhere in the Western World, Ede experienced a period of rapid economic and population growth, of mobility, increase in scale, urbanization, better education, professionalization, individualization and democratization. Developments that may be summarized in the word modernization. I wondered if modernization is an exogenous process and did it more or less just happen, or is it a planned process or something in between. I decided that the best way to answer these questions was not to study the modernization process on a national level, but on a local level. There I hoped to find the answer on the question what possibilities people have to define their own community.

I choose the municipality of Ede as my case study for the next reasons. After 1945, the Ede municipal executive opted for growth: economic, population and employment growth. In 1962, the municipal executive formulated a goal to welcome its 100,000 resident by the year 2000, which represented a doubling of the population since the end of the war. Ede was to be transformed into the city of Ede. This milestone of 100,000 inhabitants was reached as early as 1996, 60,000 of whom lived in Ede town. In order to achieve this goal, action was needed on several fronts. The rapid growth achieved was not the result of a policy plan handed down by central government. Ede was not one of the designated development areas. Ede was not regarded as an underdeveloped area requiring a top- down targeted approach for accelerated industrialization and modernization. On the other hand, in 1945, Ede was still clearly a rural community and the town centre clearly showed characteristics of a village society. So the rapid growth meant changes in different policy sectors.

Ede easily attracted new residents and employment opportunities as a result of its strategic location in the middle of the Netherlands, its good infrastructure and sufficient space. What it did need, however, was the development of housing estates and industrial estates including the necessary infrastructure and the development and expansion of, for example, education facilities and leisure amenities. In a predominantly Protestant community, this raised questions about the persuasion of these types of amenities and led to debates on, if actually desirable, the type of socio-cultural policy most appropriate for local government. Rapid expansion of a community may be perceived as a threat to the characteristics of that society. This question made Ede an extra interesting subject for research. In the case of Ede it was justifiable to assume that tensions would have arisen between the rural and urban ambitions and between Christian and secular developments. The municipal authority is involved in the developments and decision-making process relating to all the elements of the public domain, which is why it was chosen as the focus for this research.

The policy decisions required in the different areas to facilitate growth are by their nature intertwined. The construction of housing estates and business premises conflict with the interests of the agricultural sector and nature conservation. The arrival of new residents can change the social, political and religious composition of the population, resulting in consequences for how society is organized and for the future local political constellation and vice versa. Every decision must take what has occurred in other areas into account and will, in turn, have consequences for adjacent domains. For these reasons a choice was made for modernization as theoretical concept. Chapter one contains a historiographical discussion of this concept and an elaboration of how this concept has been applied to this research. In line with Schuyt and Taverne, I have chosen not to provide modernization in advance with a specific interpretation by adding ‘controlled’, ‘contested’ or ‘reflexive’. For the research, four policy areas have been selected for further investigation: spatial planning, education, guest workers/migrants and leisure facilities. As an introduction to the chapters on the developments in Ede, chapter two contains a broad outline of the national developments in which the local developments took place. Subsequently, in chapter three I discuss the way in which the modernization process was made visible in the composition of the municipal executive, including its chairpersons over a period of fifty years. Politicians not only partly determine which choices are made in the modernization process, but are also subject to this process themselves both at party and individual level. In this sense, through its decisions the political establishment in no small way contributes to determining its own future and, in turn, the composition of the municipal council and executive. The choices for more or

less growth, for public-authority or private-authority schools , for providing public amenities or not, et cetera influence who will choose Ede as a place of residence and work. In this way, secularization manifests itself in changes in the population composition and the demand for specific amenities, as well as at the level of the political composition of the municipal council and the individual councillors. As a result of the population growth, by 1966 the newcomers held the majority of the seats on the council. However, the original population of Ede managed to control the executive positions for much longer. Democratization, individualization and secularization led to an increase in the number of political parties represented on the council and enhanced pluralism. Compared to politics at national level, both women’s emancipation and the professionalization of councillors clearly had a delayed start. As was the case at national level the larger parties lost ground, although the SGP (Reformed Political Party) formed an exception in Ede.

The main theme of chapter four is spatial planning. Ede has profited considerably from the migration of residents and employment opportunities from the Randstad. Ede’s central location put it in a strategic position to benefit from national developments on spatial planning. The size of the municipality ̶ Ede being one of the largest in the Netherlands ̶ , the good infrastructure and the presence of the Veluwe National Park made Ede a popular place of residence and business. This remained the case even after, from the start of the 1960s, the provincial and national governments tried to curb the drift to Ede. As a result of its many qualities, Ede was able to achieve its growth ambitions and disregard the limiting measures imposed by higher government levels. In relation to nature conservation, Ede stayed more in line because the municipal executive regarded the Veluwe National Park as one of the attractive aspects of living in Ede. In respect to agriculture, the municipal executive chose for, on the one hand, an uncompromising policy to develop housing and business premises at the expense of farmland, while, on the other hand, applying a non-interference policy for the agricultural sector and business operations. Both small farmers and the strong growth in intensive animal husbandry could count on an accommodating local government. It was the national government which, as a result of the high levels of environmental pollution, designated the Gelderland Valley as a Spatial Planning and Environment area (ensuring spatial planning was combined with the environmental aspects). This, in turn, forced the municipal authority to impose regulatory measures on the agricultural sector in its spatial planning policies.

The policy choices in relation to the educational facilities are discussed in chapter five. What is conspicuous here is the clear commitment on the part of the Christian political parties to maintain the Christian character of the education. In the 1950s, this commitment could also count on the support of the Christian councillors representing the PvdA (Labour Party). It was not until the early 1960s that all the PvdA councillors supported the VVD (People’s Party for Freedom and Democracy) in its struggle

to increase the number of public-authority schools. In the meantime, Protestant Ede had managed, under the leadership of the ARP (Anti-Revolutionary Party) aldermen, to establish broad, and partly above municipality level, private-authority denominational schools. In achieving this, the ARP (Anti- Revolutionary Party) politicians were able to make use of their extensive network, which included national politicians. It was only in the early 1980s that secular Ede achieved a long-cherished goal with the opening of a public-authority neutral secondary school. The presence of a broad range of Protestant-Christian educational facilities is one of the explanations why Ede’s expansion did not lead to a drop, in percentage terms, of the Orthodox-Christian share of the vote. These parties were, however, practically always kept outside the coalition. Nevertheless, they managed to profit from the educational policies implemented by the coalition parties CHU (Christian Historical Union) and ARP (Anti-Revolutionary Party), and later by the CDA (Christian Democratic Appeal). These parties were not, however, rewarded for this policy as they were confronted with continuous and steady losses at the polls. Illustrative of this development was also the establishment in the 1970s of a number of Protestant Reformed primary schools and the establishment of a Protestant-Christian School Advisory Service in 1984. The long-term opposition to a more secular organization of society was also expressed in the opposition until the start of the 1970s to abolishing the dismissal of married teachers.

Ede’s growth did not only bring an influx of new residents from the rest of the Netherlands to the Veluwe. The shortage of unskilled workers, which continued to increase during the 1960s in the Netherlands, also resulted in the arrival of guest workers in Ede. Chapter six discusses the attitude of the political establishment towards this population group, whose stay was initially expected to be only temporary. It quickly became apparent that their unfamiliarity with our country, language, customs and laws in combination with their low wages and, for the most part, low level of education gave rise to a need for social assistance and specific facilities. The municipal executive did not, however, make use of the possibility to participate in the Migrant Workers’ Assistance Foundation that was established in Gelderland in the 1960s and in which the municipal executives of Apeldoorn and Arnhem participated. The Ede municipal executive maintained the view, as did other places in the Netherlands, that the

reception of this population group and the facilitating or provision of specific facilities was not the task of government —and most certainly not in the area of religion. In relation to this last point, the constitutional separation of church and state was invariably used as argumentation. Although, in practice in the Netherlands, and this includes Ede, up to that point had not been so strictly adhered to as was preached in Ede. It was only at the end of the 1970s that the first careful steps were taken to arrange for the required facilities. The municipal executive disregarded an official report in 1977 by Ede’s own Sociographical Department, in which migrant workers were considered one of the minority groups in the Netherlands and in which specific mention was made of the role of government in the origination of the problems confronting this population group. The decision of the national government in 1984 to transfer policy on minorities to local government forced the municipal executive to set down its own policy. When social unrest occurred surrounding the desire of and initiatives by the Moroccan and Turkish communities for their own place of prayer, the municipal executive slowly changed its attitude from a wait-and-see approach into an active approach in which a reasonably acceptable solution was sought in consultation with all the parties involved. The strong position of the SGP (Reformed Political Party) in local politics could present an explanation for the fact that in this period the extreme right in Ede, in contrast to national level, never achieved the electoral threshold.

Growth also places demands on leisure facilities. In the previous topics, especially in relation to the educational facilities and the facilities for migrant workers, there was an ongoing discussion in the background about how big the role of government should be in society. In confessional circles, but also within the VVD (People’s Party for Freedom and Democracy), an ideological preference prevailed for small government, meaning, where possible, the initiative should be left to the community or the individual respectively. Government spending on leisure activities was particularly sensitive in the Protestant-Christian parties. The SGP (Reformed Political Party), on principal, held the opinion that the government should not spend public money on these types of activities. The development of sport fields/sport halls and the accommodation of sports clubs could, however, count on the support of the majority of the council and certainly also of the municipal executive. In the 1950s and 1960s the aldermen of the PvdA (Labour Party), VVD (People’s Party for Freedom and Democracy) and ARP (Anti-Revolutionary Party) were great sport enthusiasts. Subsidies for cultural activities were more sensitive as theatre and opera had been a taboo for a long time within segments of the Protestant- Christian parties and, particularly, within the SGP (Reformed Political Party). If it was, nevertheless, decided to provide funding to support organizations or initiatives, then it was chosen for a strong involvement by the municipality, for example through ownership and tenures. This was an attempt by the municipal executive to exercise more control over the operations and the use of subsidies. At the same time, the municipal executive had a preference for the commercial use of, for example, a swimming pool or a theatre because this presented the possibility of keeping the public funding to a minimum. Particularly this involvement in a commercial organization gave rise, once again, to criticism within the council and within the community because commercialism with the help of public money was considered inappropriate for government and unfair competition. Ultimately, in the middle of the 1980s, the municipal executive distanced itself from the commercial operations by awarding a fixed subsidy amount based on agreements relating to the services provided to the community.

Reflecting on the fifty year period researched, two cut-off points can be established in the modernization process in Ede. The first period runs from 1945 to 1966 and is characterized by growth and tradition. The prevailing philosophy was that despite the choice for growth the Protestant-Christian character of the municipality should and could be maintained. This is illustrated in the development of a broad and above municipal level provision of private-authority Protestant-Christian educational facilities, in the commitment to non-interference in the agricultural sector including keeping the peasants, and in the conservative policy on developing cultural activities for the leisure sector.

However, the growth did strengthened aspects such as secularization, professionalization, geographical and social mobility, individualization and democratization: the modernization process continually resulted in changes in society and in the population composition and was not solely restricted to what was desirable or planned.

The second period runs to 1978 and can be characterized with the terms: change and debate.

The municipal policy was examined more critically. For example, the city-forming plans were considered undesirable both by the original population and the newcomers. Maintaining the smallness and a more rural character proved to be attractive aspects for Ede. At the same time, the demand for a more pluralistic and broader provision of social and cultural activities increased. In this second period, the non-interference policy in relation to agricultural developments except in the case that agricultural lands were required for housing and business premises, encountered opposition when the negative effects of the continuous expansion in the intensive animal husbandry for the ecology and

environment became more apparent. In addition, the arrival of migrant workers and with them Islam

into this predominantly Protestant-Christian community became more problematic during this period. As a consequence of unemployment and family reunification, more pressure was put on the municipal authorities for assistance and the need for a place of prayer for the Muslim community strengthened.

The societal and economic changes led to a more pluralistic political landscape. The six parties were confronted with increasing competition from new political parties, including the Boerenpartij (Farmers’ Party) which was the first to profit from the discontent. Only the SGP

(Reformed Political Party) managed to hold onto its share of the vote. The third period is characterized by the development of a new political situation and the search for a new political balance. The municipal executive was forced by the national government to curb the intensive animal husbandry.

The ARP (Anti-Revolutionary Party) had to part with the education portfolio and, finally, Ede got a public-authority neutral secondary school, the Pallas Athene. It was a long journey, but the Muslim community also received its own place of prayer. At a time when societal opposition to the building of a mosque appeared to favour the national extreme-right political parties and movements, the municipal executive opted to work with the Muslim groups to find a solution acceptable to all parties. The municipality distanced itself from the business operations in how it financed organizations such as swimming pools, the theatre and events such as the Week of the Heather.

What are the answers to my questions I posed in the beginning: is modernization at the local level more of less an exogenous process, can it be planned, or have local politicians enough opportunities to make a difference? When compared to the national developments it holds true for Ede that the 1950s was certainly a dynamic period, but it is also true to say that a Protestant-Christian community such as Ede required more time to shape its growth ambition so that old and new, conservative and progressive, and religious and secular could achieve a new balance and compromise. The changes were neither imposed from outside nor according to plan. The paradoxical outcome of the modernization process is that it has led to the further convergence of the local with the national developments, but it has at the same time ensured the survival of local characteristics.

Partially, these are characteristics that have consciously been or were able to be preserved by politicians, such as the predominantly Protestant-Christian education facilities and a conservative policy towards the socio-cultural domain. This policy has not, per definition, turned out favourably for the supporting political parties. It was the SGP (Reformed Political Party) and not the governing parties CHU (Christian Historical Union) and ARP (Anti-Revolutionary Party) (and later the CDA (Christian Democratic Appeal) that managed to hold onto its voters, even though the Protestant-Christian character of the municipality was the reason why a segment of the newcomers chose for Ede. Their votes did not strengthen the confessional parties at the centre of the political spectrum; it was precisely the orthodox element that benefitted, which was illustrated by the arrival of the RPF (Reformed Political Federation/GPV (Reformed Political Union). Other characteristic elements are independent of the local political policy and have ensured that Ede has become and remains a desirable place of residence and business. Its central location on the Veluwe, the good infrastructure, and the size of the municipality stimulated and made growth possible. Ede was a municipality with adequate facilities and the amenities it lacked could be found in the nearby Randstad and Arnhem.

The Veluwe National Park also forms a large, green and tranquil back garden.

Modernization was not imposed upon Ede, contrary to what Van Deursen notes in the case of Katwijk. Even so no controlled modernization for Ede, as Van Vegchel describes for Emmen. Like Zwemer states for Zeeland, local politics in Ede has been able to make a difference within the national developments and governmental guidelines. The national government only intervened and imposed their policy at the moment local political choices led to negative effects beyond the municipal boundaries. In accordance with the findings of Schuyt and Taverne the development in Ede was not the result of a ‘grand design’, not even of local politicians. Ede shows quite nice the paradox of modernization. Despite the creation of uniformity in the ongoing process of national integration and globalization, the paradox is that contradictory movements are possible that contribute to ensuring that the unique character of the area can be preserved, even if this characterization is also subject to change.

Identification and functional characterization of nonmammalian Toll-like receptor 20
Pietretti, D. ; Scheer, M.H. ; Fink, I.R. ; Taverne, N. ; Savelkoul, H.F.J. ; Spaink, H.P. ; Forlenza, M. ; Wiegertjes, G. - \ 2014
Immunogenetics 66 (2014)2. - ISSN 0093-7711 - p. 123 - 141.
carp cyprinus-carpio - leucine-rich repeats - common carp - ictalurus-punctatus - monoclonal-antibodies - pathogen recognition - accessory molecules - expression analysis - sequence-analysis - channel catfish
Like other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be subdivided into six major families, each of which recognize a general class of molecular patterns. However, there also are a number of Tlrs with unknown function, the presence of which seems unique to the bony fish, among which is Tlr20. We identified full-length complementary DNA (cDNA) sequences for tlr20 of zebrafish and common carp, two closely related fish species. Zebrafish have six copies of tlr20, whereas carp express only a single copy. Both zebrafish Tlr20 (at least Tlr20a–d) and carp Tlr20 have 26 leucine-rich repeats (LRRs). Three-dimensional modeling indicates a best fit to the crystal structure of TLR8. Phylogenetic analyses place Tlr20 in the TLR11 family closest to Tlr11 and Tlr12, which sense ligands from protozoan parasites in the mouse. Conservation of genes on zebrafish chromosome 9, which carries tlr20, with genes on mouse chromosome 14, which carries tlr11, indicates Tlr11 could be a possible ortholog of Tlr20. Confocal microscopy suggests a subcellular localization of Tlr20 at the endoplasmatic reticulum. Although in vitro reporter assays could not identify a ligand unique to Tlr20, in vivo infection experiments indicate a role for Tlr20 in the immune response of carp to protozoan parasites (Trypanoplasma borreli). Carp tlr20 is mainly expressed in peripheral blood leukocytes (PBL) with B lymphocytes, in particular, expressing relatively high levels of Tlr20. In vitro stimulation of PBL with T. borreli induces an upregulation of tlr20, supportive of a role for Tlr20 in the immune response to protozoan parasites.
Consumption of antimicrobials in pigs, veal calves, and broilers in the Netherlands: Quantitative results of nationwide collection of data in 2011
Bos, M.E.H. ; Taverne, F.J. ; Geijlswijk, I.M. van; Mouton, J.W. ; Mevius, D.J. ; Heederik, D.J.J. - \ 2013
PLoS ONE 8 (2013)10. - ISSN 1932-6203 - 9 p.
resistant staphylococcus-aureus - escherichia-coli - animals - farmers - health - costs - herds - usage - meat - food
In 2011, Dutch animal production sectors started recording veterinary antimicrobial consumption. These data are used by the Netherlands Veterinary Medicines Authority to create transparency in and define benchmark indicators for veterinary consumption of antimicrobials. This paper presents the results of sector wide consumption of antimicrobials, in the form of prescriptions or deliveries, for all pig, veal calf, and broiler farms. Data were used to calculate animal defined daily dosages per year (ADDD/Y) per pig or veal calf farm. For broiler farms, number of animal treatment days per year was calculated. Furthermore, data were used to calculate the consumption of specific antimicrobial classes per administration route per pig or veal calf farm. The distribution of antimicrobial consumption per farm varied greatly within and between farm categories. All categories, except for rosé starter farms, showed a highly right skewed distribution with a long tail. Median ADDD/Y values varied from 1.2 ADDD/Y for rosé finisher farms to 83.2 ADDD/Y for rosé starter farms, with 28.6 ADDD/Y for white veal calf farms. Median consumption in pig farms was 9.3 ADDD/Y for production pig farms and 3.0 ADDD/Y for slaughter pig farms. Median consumption in broiler farms was 20.9 ATD/Y. Regarding specific antimicrobial classes, fluoroquinolones were mainly used on veal calf farms, but in low quantities: P75 range was 0 – 0.99 ADDD/Y, and 0 – 0.04 ADDD/Y in pig farms. The P75 range for 3rd/4th-generation cephalosporins was 0 – 0.07 ADDD/Y for veal calf farms, and 0 – 0.1 ADDD/Y for pig farms. The insights obtained from these results, and the full transparency obtained by monitoring antimicrobial consumption per farm, will help reduce antimicrobial consumption and endorse antimicrobial stewardship. The wide and skewed distribution in consumption has important practical and methodological implications for benchmarking, surveillance and future analysis of trends.
Immunomodulatory effects of streptococcus suis capsule type on human dendritic cell responses, phagocytosis and intracellular survival.
Meijerink, M. ; Ferrando, M.L. ; Lammers, G. ; Taverne, N. ; Smith, H.E. ; Wells, J. - \ 2012
PLoS ONE 7 (2012)4. - ISSN 1932-6203
in-vivo - zoonotic pathogen - genetic diversity - dc-sign - group-b - virulence - serotype-2 - pigs - polysaccharide - strains
Streptococcus suis is a major porcine pathogen of significant commercial importance worldwide and an emerging zoonotic pathogen of humans. Given the important sentinel role of mucosal dendritic cells and their importance in induction of T cell responses we investigated the effect of different S. suis serotype strains and an isogenic capsule mutant of serotype 2 on the maturation, activation and expression of IL-10, IL-12p70 and TNF-a in human monocyte-derived dendritic cells. Additionally, we compared phagocytosis levels and bacterial survival after internalization. The capsule of serotype 2, the most common serotype associated with infection in humans and pigs, was highly anti-phagocytic and modulated the IL-10/IL-12 and IL-10/TNF-a cytokine production in favor of a more anti-inflammatory profile compared to other serotypes. This may have consequences for the induction of effective immunity to S. suis serotype 2 in humans. A shielding effect of the capsule on innate Toll-like receptor signaling was also demonstrated. Furthermore, we showed that 24 h after phagocytosis, significant numbers of viable intracellular S. suis were still present intracellularly. This may contribute to the dissemination of S. suis in the body.
Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface glycan composition and host cell signaling
Remus, D.M. ; Kranenburg, R. van; Swam, I.I. van; Taverne, N. ; Bongers, R.S. ; Wels, M. ; Wells, J. ; Bron, P.A. ; Kleerebezem, M. - \ 2012
Microbial Cell Factories 11 (2012)1. - ISSN 1475-2859 - 10 p.
lactic-acid bacteria - gene-expression omnibus - streptococcus-pneumoniae - lactococcus-lactis - exopolysaccharide biosynthesis - microarray data - subsp cremoris - rhamnosus gg - identification - strains
Background - Bacterial cell surface-associated polysaccharides are involved in the interactions of bacteria with their environment and play an important role in the communication between pathogenic bacteria and their host organisms. Cell surface polysaccharides of probiotic species are far less well described. Therefore, improved knowledge on these molecules is potentially of great importance to understand the strain-specific and proposed beneficial modes of probiotic action. Results - The Lactobacillus plantarum WCFS1 genome encodes 4 clusters of genes that are associated with surface polysaccharide production. Two of these clusters appear to encode all functions required for capsular polysaccharide formation (cps2A-J and cps4A-J), while the remaining clusters are predicted to lack genes encoding chain-length control functions and a priming glycosyl-transferase (cps1A-I and cps3A-J). We constructed L. plantarum WCFS1 gene deletion mutants that lack individual (¿cps1A-I, ¿cps2A-J, ¿cps3A-J and ¿cps4A-J) or combinations of cps clusters (¿cps1A-3J and ¿cps1A-3I, ¿cps4A-J) and assessed the genome wide impact of these mutations by transcriptome analysis. The cps cluster deletions influenced the expression of variable gene sets in the individual cps cluster mutants, but also considerable numbers of up- and down-regulated genes were shared between mutants in cps cluster 1 and 2, as well as between mutant in cps clusters 3 and 4. Additionally, the composition of overall cell surface polysaccharide fractions was altered in each mutant strain, implying that despite the apparent incompleteness of cps1A-I and cps3A-J, all clusters are active and functional in L. plantarum. The ¿cps1A-I strain produced surface polysaccharides in equal amounts as compared to the wild-type strain, while the polysaccharides were characterized by a reduced molar mass and the lack of rhamnose. The mutants that lacked functional copies of cps2A-J, cps3A-J or cps4A-J produced decreased levels of surface polysaccharides, whereas the molar mass and the composition of polysaccharides was not affected by these cluster mutations. In the quadruple mutant, the amount of surface polysaccharides was strongly reduced. The impact of the cps cluster mutations on toll-like receptor (TLR)-mediated human nuclear factor (NF)-¿B activation in host cells was evaluated using a TLR2 reporter cell line. In comparison to a L. plantarum wild-type derivative, TLR2 activation remained unaffected by the ¿cps1A-I and ¿cps3A-J mutants but appeared slightly increased after stimulation with the ¿cps2A-J and ¿cps4A-J mutants, while the ¿cps1A-3J and ¿cps1A-3J, ¿cps4A-J mutants elicited the strongest responses and clearly displayed enhanced TLR2 signaling. Conclusions - Our study reveals that modulation of surface glycan characteristics in L. plantarum highlights the role of these molecules in shielding of cell envelope embedded host receptor ligands. Although the apparently complete cps clusters (cps2A-J and cps4A-J) contributed individually to this shielding, the removal of all cps clusters led to the strongest signaling enhancement. Our findings provide new insights into cell surface glycan biosynthesis in L. plantarum, which bears relevance in the context of host-cell signaling by probiotic bacteria.
Immunomodulatory effects of potential probiotics in a mouse peanut sensitization model
Meijerink, M. ; Wells, J. ; Taverne, N. ; Zeeuw Brouwer, M.L. de; Hilhorst, B. ; Venema, K. ; Bilsen, J. van - \ 2012
FEMS Immunology and Medical Microbiology 65 (2012)3. - ISSN 0928-8244 - p. 488 - 496.
lactic-acid bacteria - placebo-controlled trial - regulatory t-cells - blood mononuclear-cells - atopic-dermatitis - dendritic cells - food allergy - lactobacillus-rhamnosus - cytokine production - responses
Peanut allergy accounts for the majority of severe food-related allergic reactions and there is a need for new prevention and treatment strategies. Probiotics may be considered for treatment on the basis of their immunomodulating properties. Cytokine profiles of probiotic strains were determined by in vitro co-culture with human PBMCs. Three strains were selected to investigate their prophylactic potential in a peanut sensitization model by analysing peanut-specific antibodies, mast cell degranulation and ex vivo cytokine production by splenocytes. The probiotic strains induced highly variable cytokine profiles in PBMCs. L. salivarius HMI001, L. casei Shirota (LCS) and L. plantarum WCFS1 were selected for further investigation owing to their distinct cytokine patterns. Prophylactic treatment with both HMI001 and LCS attenuated the Th2 phenotype (reduced mast cell responses and ex vivo IL-4 and/or IL-5 production). In contrast, WCFS1 augmented the Th2 phenotype (increased mast cell and antibody responses and ex vivo IL-4 production). In vitro PBMC screening was useful in selecting strains with anti-inflammatory and Th1 skewing properties. In case of HMI001 (high IL-10/IL-12 ratio) and LCS (high interferon- and IL-12), partial protection was seen in a mouse peanut allergy model. Strikingly, certain strains may worsen the allergic reaction as shown in the case of WCFS1.
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