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.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    A20 contribution to NF-κB regulation, Ripoptosome formation and TNF-induced cell death
    Hooiveld, Guido - \ 2020
    Wageningen University
    Homo sapiens - Mus musculus - GSE128249 - PRJNA526879
    This SuperSeries is composed of the SubSeries listed below
    Fat_challenge_tests
    Matualatupauw, Juri ; Bouwman, Jildau - \ 2020
    Wageningen University
    GSE124534 - PRJNA512449 - Homo sapiens
    Exploration of new markers that define impaired metabolic flexibility using an acute postprandial challenge test. Healthy subjects underwent a 4-week high-fat high-calorie diet. High-fat challenges were performed in these subjects before and after the diet and in subjects with the metabolic syndrome.
    The host response of IBS patients to allogenic and autologous faecal microbiota transfer
    Holster, Savanne ; Hooiveld, G.J.E.J. ; Brummer, Robert-Jan ; König, Julia - \ 2019
    Wageningen University
    GSE138297 - Homo sapiens - PRJNA575360
    In this randomised placebo-controlled trial, irritable bowel syndrome (IBS) patients were treated with faecal material from a healthy donor (n=8, allogenic FMT) or with their own faecal microbiota (n=8, autologous FMT). The faecal transplant was administered by whole colonoscopy into the caecum (30 g of stool in 150 ml sterile saline). Two weeks before the FMT (baseline) as well as two and eight weeks after the FMT, the participants underwent a sigmoidoscopy, and biopsies were collected at a standardised location (20-25 cm from the anal verge at the crossing with the arteria iliaca communis) from an uncleansed sigmoid. In patients treated with allogenic FMT, predominantly immune response-related genes sets were induced, with the strongest response two weeks after FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected.
    Transcriptome as marker for nutrition-related health: added value of time course analyses during challenge tests before and after energy restriction
    Hooiveld, G.J.E.J. ; Bussel, I.P.G. van; Fazelzadeh, P. ; Frost, G.S. ; Afman, L.A. - \ 2019
    Wageningen University
    Homo sapiens - GSE88794 - PRJNA348614
    Phenotypic flexibility is used as a measure for health and can be studied during nutritional challenge tests. Changes in gene expression are early markers and give insight into mechanisms. Energy restriction (ER) has a variety of beneficial health effects and can be used to investigate different health states to study postprandial changes during challenge tests. Objective: We aimed to determine the postprandial effects of a 20% ER diet on whole genome expression profiles of peripheral blood mononuclear cells (PBMCs). Materials and methods: 72 healthy, overweight men and women, aged 50-65, were subjected to an oral glucose tolerance test (OGTT) and a mixed meal test (MMT), before and after a 12 week intervention with either a 20% ER diet or a control diet. Total RNA from PBMCs was isolated at fasting, and at postprandially during the OGTT at 30, 60, and 120 min and during the MMT at 60, 120, 240, and 360 min. RNA of all time points was used to evaluate whole genome gene expression response using Affymetrix microarrays, resulting in a number of 1231 arrays. Results and conclusions: Upon 20% ER, gene sets involved in OXPHOS, cell adhesion, energy metabolism, immune system, cell cycle, and DNA replication were increased. Upon an OGTT, OXPHOS, cell adhesion, and DNA replication gene sets were decreased after ER. Also, some postprandial effects seem to happen in the control group, but at a later stage. We concluded that ER increased phenotypic flexibility by means on increased use of OXPHOS pathways, and that the response to an OGTT seemed faster upon ER than upon a control diet
    No effect of calcifediol supplementation on skeletal muscle transcriptome in vitamin D deficient frail older adults
    Hangelbroek, R.W.J. ; Vaes, A.M.M. ; Boekschoten, M.V. ; Hooiveld, G.J.E.J. ; Kersten, A.H. - \ 2019
    Wageningen University
    GSE123993 - Homo sapiens - PRJNA510436
    Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults.
    Gut microbiota structure in the course of pediatric allo-HSCT
    Bekker, Vincent ; Zwittink, Romy ; Knetsch, Cornelis W. ; Sanders, Ingrid M.J.G. ; Berghuis, Dagmar ; Heidt, Peter J. ; Vossen, Jaak M.J.J. ; Vos, Willem de; Belzer, Clara ; Bredius, Robbert G.M. ; van‘t Hof, Peter J. ; Lankester, Arjan C. ; Kuijper, Ed J. - \ 2018
    Leiden University Medical Centre
    PRJEB28845 - ERP111102 - Homo sapiens
    Effect of selective and total gut decontamination treatments on gut microbiota structure in the course of pediatric allogenic HSCT, as determined via 16S rRNA gene amplicon sequencing.
    Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants
    Korpela, Katri ; Salonen, Anne ; Vepsäläinen, Outi ; Suomalainen, Marjo ; Kolmeder, Carolin ; Varjosalo, Markku ; Miettinen, Sini ; Kukkonen, Kaarina ; Savilahti, Erkki ; Kuitunen, Mikael ; Vos, Willem de - \ 2018
    University of Helsinki
    PRJEB27325 - ERP109395 - Homo sapiens
    Background: Infants born by caesarean section or receiving antibiotics are at increased risk of developing metabolic, inflammatory and immunological diseases, potentially due to disruption of normal gut microbiota at a critical developmental time window. We investigated whether probiotic supplementation could ameliorate the effects of antibiotic use or caesarean birth on infant microbiota in a double blind, placebo- controlled randomized clinical trial. Mothers were given a multispecies probiotic, consisting of Bifidobacterium, Lactobacillus, and Propionibacterium strains, or placebo supplement during pregnancy and the infants were given the same supplement. Fecal samples of the infants were collected at 3 months and analyzed using taxonomic, metagenomic and metaproteomic approaches.Results: The probiotic supplement had a strong overall impact on the microbiota composition, but the effect depended on the infant's diet. Only breastfed infants showed the expected increase in bifidobacteria and reduction in Proteobacteria and Clostridia. In the placebo group, both birth mode and antibiotic use were significantly associated with altered microbiota composition and function, particularly reduced Bifidobacterium abundance. In the probiotic group, the effects of antibiotics and birth mode were either completely eliminated or reduced.Conclusions: The results indicate that it is possible to correct undesired changes in microbiota composition and function caused by antibiotic treatments or caesarean birth by supplementing infants with a probiotic mixture together with at least partial breastfeeding.
    The effect of probiotic Lactobacilli strains, inulin-type fructans and oligofructose on gene expression profiles in intestinal Caco-2 cells
    Wit, N.J.W. de; Lepine, Alexia ; Boekschoten, M.V. ; Mes, J.J. - \ 2018
    GSE115022 - Homo sapiens - PRJNA473527
    Background: Beneficial microbes can be actors in maintaining or stimulating barrier function, and may counteract pathogen-infection. Lactobacilli are particularly recognized for enhancing intestinal barrier function and to confer protective effects against multiresistant pathogens. Various L. acidophilus strains support intestinal immune barrier function and have been shown to improve resistance to pathogens. Although less extensively studied than beneficial bacteria, other food-based ingredients that can contribute to strengthening barrier function are dietary fibers. For instance, inulin and fructooligosaccharides (FOS) have recently been shown to enhance barrier function and protect against barrier dysfunction. Effects of these ingredients on intestinal barrier function were evaluated by quantifying regulation of gene expression by microarray. Methods: Caco-2 cells were incubated with probiotic strains or inulin-type fibers for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. Results: Only L. acidophilus modulated a group of 26 genes related to tight-junctions. Inulin-type fructans, L. brevis W63 and L. casei W56 regulated other genes, unrelated to tight junctions. L. acidophilus also had unique effects on a group of 6 genes regulating epithelial phenotype towards follicle-associated epithelium. L. acidophilus W37 was therefore selected for a challenge with STM and prevented STM-induced barrier disruption and decreased secretion of IL-8. L. acidophilus W37 increases TEER and can protect against STM induced disruption of gut epithelial cells integrity in vitro. Conclusion: Our results suggest that selection of specific bacterial strains for enforcing barrier function may be a promising strategy to reduce or prevent STM infections.
    Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness
    Hangelbroek, R.W.J. ; Fazelzadeh, P. ; Tieland, C.A.B. ; Boekschoten, M.V. ; Hooiveld, G.J.E.J. ; Duynhoven, J.P.M. van; Timmons, James ; Verdijk, L. ; Groot, C.P.G.M. de; Loon, L.J.C. van; Müller, M.R. - \ 2018
    Wageningen University
    GSE117525 - Homo sapiens - PRJNA482398
    The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle.
    Circadian misalignment induces fatty acid metabolism gene profiles and induces insulin resistance in human skeletal muscle
    Wefers, Jakob ; Moorsel, Dirk van; Hansen, Jan ; Hooiveld, G.J.E.J. ; Kersten, A.H. ; Schrauwen, Patrick - \ 2018
    Wageningen University
    GSE106800 - Homo sapiens - PRJNA418092
    Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes, however, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and muscle molecular circadian clock have never been investigated in humans. Here we investigated insulin sensitivity and muscle metabolism in fourteen healthy young lean men (age 22.4 ± 2.8 years; BMI 22.3 ± 2.1 kg/m2 [mean ± SD]) after a 3-day control protocol and a 3.5-day misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that circadian misalignment results in a significant decrease in peripheral insulin sensitivity due to a reduced skeletal muscle non-oxidative glucose disposal (Rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg/min; control vs. misalignment; p=0.024). Fasting glucose and FFA levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the new behavourial rhythm, and microarray analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misallignement. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.
    Pure epicatechin and inflammatory gene expression profiles in circulating immune cells in (pre) hypertensive adults; a randomized double-blind, placebo-controlled, crossover trial
    Esser, D. ; Dower, J.I. ; Matualatupauw, J.C. ; Geleijnse, J.M. ; Kromhout, D. ; Hollman, P.C.H. ; Afman, L.A. - \ 2018
    Wageningen University
    Homo sapiens - GSE84453 - PRJNA329219
    Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health.
    Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans
    Vink, R.G. ; Roumans, N.J. ; Fazelzadeh, Parastoo ; Tareen, S.H. ; Boekschoten, Mark ; Mariman, E.C. ; Baak, M.A. van - \ 2017
    Wageningen University
    Homo sapiens - GSE77962 - Homo sapiens - GSE77962 - PRJNA312210
    Background: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown.
    A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate
    Gils-Kok, Dieuwertje van; Kiemeney, Lambertus A.L.M. ; Verhaegh, Gerald W. ; Schalken, Jack A. ; Lin, Emile N.J.T. van; Sedelaar, J.P.M. ; Witjes, J.A. ; Hulsbergen-van de Kaa, Christina A. ; Veer, Pieter van 't; Kampman, Ellen ; Afman, Lydia - \ 2017
    Wageningen University
    GSE77959 - Homo sapiens - GSE77959 - Homo sapiens - PRJNA312203
    In parallel with the inconsistency in observational studies and chemoprevention trials, the molecular mechanisms by which selenium may affect prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled intervention trial to examine the effects of a short-term intervention with selenized yeast on whole-genome expression profiles in non-malignant prostate tissue. Twenty-three men receiving prostate biopsies were randomly assigned to take 300 µg selenized yeast per day (n=12) or placebo (non-selenized yeast, n=11) during a median intervention period of 35 (interquartile range: 31-35) days. Prostate specimens, collected from the transition zone before and after intervention, of 15 participants (n=8 selenium, n=7 placebo) were available for analysis using Affymetrix GeneChip Human 1.0 ST Arrays. Pathway and gene set enrichment analyses revealed that the intervention with selenium resulted in a down-regulated expression of genes involved in signaling pathways related to cellular adhesion, migration, invasion, remodeling and immune responses. Specifically, expression of the well-established epithelial marker E-cadherin was up-regulated, while mesenchymal markers, such as vimentin and fibronectin, were down-regulated after the intervention with selenium. This implies an effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium affected expression of genes involved in wound healing and inflammation, processes which are both related to EMT. In conclusion, our data showed that selenium affected expression of genes implicated in EMT, mainly represented by a change in the direction of the epithelial rather than the mesenchymal phenotype.
    Association between DNA methylation profiles in leukocytes and serum levels of persistent organic pollutants in Dutch men
    Dungen, Myrthe van den; Murk, Tinka ; Kampman, Ellen ; Steegenga, Wilma ; Gils-Kok, Dieuwertje van - \ 2017
    Homo sapiens - GSE79329 - PRJNA315514
    Genome-wide DNA methylation profiling was performed in Dutch men consuming eel from relatively low- or high-polluted areas, resulting in a broad range of serum POP levels. The Illumina Infinium 450K Human DNA methylation Beadchip v1.0HD was used to measure DNA methylation in these men and associate this with serum levels of persistent organic pollutants (POPs). In total 48 POPs were measured, of which 30 POPs had levels above the detection limit in at least 60% of the participants. Furthermore, 11 different clinical parameters were measured as biomarkers for health. The leukocyte count was measured in each sample to adjust DNA methylation values. Furthermore, participants reported possible confounders in a questionnaire.
    The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial
    Mujagic, Zlatan ; Vos, Paul de; Boekschoten, Mark ; Govers, Coen ; Pieters, Harm J.H.M. ; Wit, Nicole de; Bron, Peter A. ; Masclee, Ad A.M. ; Troost, Freddy J. - \ 2017
    Wageningen University
    Homo sapiens - GSE74988 - Homo sapiens - GSE74988 - PRJNA302145
    The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450) or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06±0.04 to 0.10±0.06, p=0.001), but was not significantly affected by the bacterial interventions. However, gene transcription pathway analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific effects on repair processes in the compromised intestine of healthy subjects.
    Changes over lactation in breast milk serum proteins
    Zhang, L. ; Waard, Marita de; Verheijen, Hester ; Boeren, Sjef ; Hageman, J.A. ; Hooijdonk, A.C.M. van; Vervoort, J.J.M. ; Goudoever, Johannes B. van; Hettinga, K.A. - \ 2016
    Wageningen University & Research
    Homo sapiens - PXD003465 - milk - Milk serum proteome
    The objective of this study is to investigate the changes of the breast milk proteome from four individual mothers over a six month lactation period by shotgun proteomic techniques, because a comprehensive understanding of the human milk proteome may lead to better understanding of the needs of infants. This may contribute to the improvement of infant formula.
    Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions
    Versluis, D. ; Andrea, M.M. D'; Ramiro Garcia, J. ; Leimena, M.M. ; Hugenholtz, F. ; Zhang, J. ; Ozturk, Basak ; Nylund, L. ; Sipkema, D. ; Schaik, W. van; Vos, W.M. de; Kleerebezem, M. ; Smidt, H. ; Passel, M.W.J. van - \ 2016
    Wageningen University
    PRJEB7599 - PRJEB7599 - Sus scrofa - Homo sapiens - Crambe crambe - Mus musculus
    We use a novel approach (an analysis of metatranscriptomics data) to study antibiotic resistance, a topic that poses major health care concerns. We investigate resistance gene expression in microbial communities in a diverse range of environments.
    Macrophage heterogeneity in human carotid artery atherosclerotic plaques: identification of novel markers for M1 and M2 that are independent of the activation status
    Tits, L.J. van; Stienstra, Rinke ; Netea, M.G. ; Pol, J.A. ; Truijers, M. ; Vliet, J.A. van der; Hooiveld, Guido ; Joosten, L.A. ; Stalenhoef, A.F. - \ 2016
    Wageningen University
    GSE22543 - Homo sapiens - PRJNA128169 - GSE22543 - Homo sapiens - PRJNA128169
    Recent studies suggest the presence of both “classically activated” M1 and “alternatively activated” M2 macrophages in human atherosclerotic tissue, yet due to the lack of validated markers the reported localization patterns of these macrophage phenotypes within plaques are ambiguous. In the present study, we searched for markers that indisputably can identify differentiated M1 and M2 macrophages independently of stimuli that affect the activation status of the two subpopulations. We used these validated markers to assess the presence of M1 and M2 macrophages in different zones of human carotid artery atherosclerotic plaques obtained from 12 patients. Using microarray and qPCR technology we show that the frequently used macrophage subpopulation markers MCP-1 and CD206 do not discriminate between M1 and M2 macrophages. However, we confirm the subtype specificity of the classical M2 marker CD163 and we report that the genes INHBA and DSP (both M1) and SEPP1 and MARCKS (both M2) are highly suitable for macrophage phenotyping. mRNA expression of the pan-macrophage marker CD68 in the shoulder zones of the plaques and in adjacent tissue segments correlated positively with mRNA expression levels of SEPP1, MARCKS and CD163 (r=0.86, 0.94 and 0.96, and r= 0.86, 0.98 and 0.69, respectively) but not with the expression of the M1 markers DSP and INHBA. In contrast, mRNA expression of CD68 in the core of the plaques correlated positively with expression of DSP and INHBA (r=0.73 and 0.49) but not with SEPP1, MARCKS and CD163. These findings suggest that M1 macrophages predominate in the core of human carotid atherosclerotic plaques while M2 macrophages prevail at the periphery of the plaque.
    Innate Immune Recognition of Bacterial Viability Instructs Human T follicular Helper Cell Differentiation
    Valai, Atijeh ; Ugolini, Matteo ; Gerhard, Jenny ; Georg, Philipp ; Helbig, Elisa T. ; Opitz, Bastian ; Kurth, Florian ; Boekschoten, Mark ; Muller, Michael ; Suttorp, Norbert ; Sander, Leif E. - \ 2016
    Wageningen University
    GSE68255 - Homo sapiens - PRJNA282140 - GSE68255 - Homo sapiens - PRJNA282140
    Live attenuated vaccines are often superior to dead vaccines, yet the immunological mechanisms remain largely obscure. We have recently uncovered an inherent capacity of antigen-presenting cells (APC) to discriminate live from killed bacteria by virtue of vita-PAMPs. Here we found that innate recognition of bacterial viability strongly promotes the differentiation of fully functional T follicular helper (TFH) cells. We identify TLR8 and its signaling adaptor MyD88 as critical sensor for bacterial viability in human APC, activation of which is required and sufficient to induce selective transcriptional remodeling and the production of TFH promoting signals like IL-12. Activators of other TLRs including licensed vaccine adjuvants fail to do so. Consequently, vita-PAMP receptors such as TLR8 represent promising targets for adjuvants to improve the efficacy of modern inanimate subunit vaccines.
    Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid
    IJssenagger, N. ; Janssen, A.W.F. ; Kersten, A.H. ; Mil, S.W.C. van - \ 2016
    Wageningen University
    Homo sapiens - Mus musculus - GSE76163 - PRJNA306501
    This SuperSeries is composed of the SubSeries listed below.
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