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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    Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis
    Domínguez-Andrés, Jorge ; Arts, Rob J.W. ; Horst, Rob ter; Gresnigt, Mark S. ; Smeekens, Sanne P. ; Ratter, Jacqueline M. ; Lachmandas, Ekta ; Boutens, Lily ; Veerdonk, Frank L. van de; Joosten, Leo A.B. ; Notebaart, Richard A. ; Ardavín, Carlos ; Netea, Mihai G. - \ 2017
    PLoS Pathogens 13 (2017)9. - ISSN 1553-7366 - 23 p.

    Monocytes are innate immune cells that play a pivotal role in antifungal immunity, but little is known regarding the cellular metabolic events that regulate their function during infection. Using complementary transcriptomic and immunological studies in human primary monocytes, we show that activation of monocytes by Candida albicans yeast and hyphae was accompanied by metabolic rewiring induced through C-type lectin-signaling pathways. We describe that the innate immune responses against Candida yeast are energy-demanding processes that lead to the mobilization of intracellular metabolite pools and require induction of glucose metabolism, oxidative phosphorylation and glutaminolysis, while responses to hyphae primarily rely on glycolysis. Experimental models of systemic candidiasis models validated a central role for glucose metabolism in anti-Candida immunity, as the impairment of glycolysis led to increased susceptibility in mice. Collectively, these data highlight the importance of understanding the complex network of metabolic responses triggered during infections, and unveil new potential targets for therapeutic approaches against fungal diseases.

    Understanding human immune function using the resources from the Human Functional Genomics Project
    Netea, Mihai G. ; Joosten, Leo A.B. ; Li, Yang ; Kumar, Vinod ; Oosting, Marije ; Smeekens, Sanne ; Jaeger, Martin ; Horst, Rob Ter; Schirmer, Melanie ; Vlamakis, Hera ; Notebaart, Richard ; Pavelka, Norman ; Aguirre-Gamboa, Raul Raul ; Swertz, Morris A. ; Tunjungputri, Rahajeng N. ; De Heijden, Wouter Van; Franzosa, Eric A. ; Ng, Aylwin ; Graham, Daniel ; Lassen, Kara ; Schraa, Kiki ; Netea-Maier, Romana ; Smit, Jan ; Mast, Quirijn De; De Veerdonk, Frank Van; Kullberg, Bart Jan ; Tack, Cees ; De Munckhof, Inge Van; Rutten, Joost ; Graaf, Jacqueline Van Der; Franke, Lude ; Hofker, Marten ; Jonkers, Iris ; Platteel, Mathieu ; Maatman, Astrid ; Fu, Jingyuan ; Zhernakova, Alexandra ; Meer, Jos W.M. Van Der; Dinarello, Charles A. ; Ven, Andre Van Der; Huttenhouwer, Curtis ; Koenen, Hans ; Joosten, Irma ; Xavier, Ramnik J. ; Wijmenga, Cisca - \ 2016
    Nature Medicine 22 (2016)8. - ISSN 1078-8956 - p. 831 - 833.
    Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity
    Arts, Rob J.W. ; Novakovic, Boris ; Horst, Rob ter; Carvalho, Agostinho ; Bekkering, Siroon ; Lachmandas, Ekta ; Rodrigues, Fernando ; Silvestre, Ricardo ; Cheng, Shih Chin ; Wang, Shuang Yin ; Habibi, Ehsan ; Gonçalves, Luís G. ; Mesquita, Inês ; Cunha, Cristina ; Laarhoven, Arjan van; Veerdonk, Frank L. van de; Williams, David L. ; Meer, Jos W.M. van der; Logie, Colin ; O'Neill, Luke A. ; Dinarello, Charles A. ; Riksen, Niels P. ; Crevel, Reinout van; Clish, Clary ; Notebaart, Richard A. ; Joosten, Leo A.B. ; Stunnenberg, Hendrik G. ; Xavier, Ramnik J. ; Netea, Mihai G. - \ 2016
    Cell Metabolism 24 (2016)6. - ISSN 1550-4131 - p. 807 - 819.
    cholesterol metabolism - epigenetics - glutamine metabolism - glycolysis - trained immunity

    Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to β-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.

    In-host adaptation and acquired triazole resistance in Aspergillus fumigatus: a dilemma for clinical management
    Verweij, P. ; Zhang, J. ; Debets, A.J.M. ; Meis, J.F. ; Schoustra, S.E. ; Veerdonk, F.L. van de; Zwaan, B.J. ; Melchers, W.J.G. - \ 2016
    The Lancet Infectious Diseases 16 (2016)11. - ISSN 1473-3099 - p. e251 - e260.
    Aspergillus fumigatus causes a range of diseases in human beings, some of which are characterised by fungal persistence. A fumigatus can persist by adapting to the human lung environment through physiological and genomic changes. The physiological changes are based on the large biochemical versatility of the fungus, and the genomic changes are based on the capacity of the fungus to generate genetic diversity by spontaneous mutations or recombination and subsequent selection of the genotypes that are most adapted to the new environment. In this Review, we explore the adaptation strategies of A fumigatus in relation to azole resistance selection and the clinical implications thereof for management of diseases caused by Aspergillus spp. We hypothesise that the current diagnostic tools and treatment strategies do not take into account the biology of the fungus and might result in an increased likelihood of fungal persistence in patients. Stress factors, such as triazole exposure, cause mutations that render resistance. The process of reproduction-ie, sexual, parasexual, or asexual-is probably crucial for the adaptive potential of Aspergillus spp. As any change in the environment can provoke adaptation, switching between triazoles in patients with chronic pulmonary aspergillosis might result in a high-level pan-triazole-resistant phenotype through the accumulation of resistance mutations. Alternatively, when triazole therapy is stopped, an azole-free environment is created that could prompt selection for compensatory mutations that overcome any fitness costs that are expected to accompany resistance development. As a consequence, starting, switching, and stopping azole therapy has the risk of selecting for highly resistant strains with wildtype fitness. A similar adaptation is expected to occur in response to other stress factors, such as endogenous antimicrobial peptides; over time the fungus will become increasingly adapted to the lung environment, thereby limiting the probability of eradication. Our hypothesis challenges current management strategies, and future research should investigate the genomic dynamics during infection to understand the key factors facilitating adaptation of Aspergillus spp.
    The inflammasome is a central player in the induction of obesity and insulin resistance
    Stienstra, Rinke ; Diepen, Janna A. van; Tack, Cees J. ; Zaki, Mohammad H. ; Veerdonk, Frank L. van de; Perera, Deshani ; Neal, Geoff ; Hijmans, Anneke ; Vroegrijk, Irene O. ; Berg, Sjoerd A. van den; Romijn, Johannes A. ; Rensen, Patrick C. ; Joosten, Leo A. ; Netea, Mihai G. ; Kanneganti, Thirumala-Devi D. - \ 2011
    Wageningen University
    GSE25205 - Mus musculus - PRJNA134319 - GSE25205 - Mus musculus - PRJNA134319
    Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in pro-inflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3 [NLR family, pyrin domain containing 3] resulting in caspase-1 activation and production of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Here, we showed that mice deficient in Nlrp3, ASC [apoptosis-associated speck-like protein containing a CARD; a.k.a PYCARD (PYD and CARD domain containing)] and caspase-1 were resistant to the development of high fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance and suggest inhibition of the inflammasome as a potential therapeutic strategy.
    Inflammasome is a central player in the induction of obesity and insulin resistance
    Stienstra, R. ; Diepen, J.A. van; Tack, C.J. ; Zaki, M.H. ; Veerdonk, F.L. van de; Perera, D. ; Neale, G.A. ; Hooiveld, G.J.E.J. ; Hijmans, A. ; Vroegrijk, I. ; Berg, S. ; Romijn, J. ; Rensen, P.C.N. ; Joosten, L.A.B. ; Netea, M.G. ; Kanneganti, T.D. - \ 2011
    Proceedings of the National Academy of Sciences of the United States of America 108 (2011)37. - ISSN 0027-8424 - p. 15324 - 15329.
    adipose-tissue - mice deficient - caspase-1 - interleukin-18 - expression - sensitivity - activation - il-1-beta - apoptosis - crystals
    Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1 beta and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy.
    Voedingsmiddelen dreigen afhandeling weborders te bederven
    Veerdonk, W. van de - \ 2001
    Voedingsmiddelentechnologie 34 (2001)5. - ISSN 0042-7934 - p. 41 - 43.
    dienstensector - gemaksvoedsel - kant-en-klaarvoedsel - voedingsmiddelen - elektronica - computers - geïntegreerde circuits - marketingkanalen - verkooptechniek - internet - logistiek - bedrijfseconomie - services - convenience foods - instant foods - foods - electronics - computers - integrated circuits - marketing channels - salesmanship - internet - logistics - business management
    De virtuele verkoop van levensmiddelen. Het systeem moet niet alleen kostenefficient zijn maar moet ook de voedselveiligheid en de productkwaliteit garanderen
    Schakels : supply chain analyse kwaliteit, economie en logistiek in de voedingstuinbouw, de kleding en de cosmetica
    Veerdonk, W.J.A.A. van de - \ 2000
    Wageningen etc. : ATO [etc.] - 63
    kettingen - economie - kwaliteit - kleding - tuinbouw - cosmetica - voedselindustrie - chains - economics - quality - clothing - horticulture - cosmetics - food industry
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