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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Nutrition of pigs kept under low and high sanitary conditions : effects on animo acid and energy metabolism and damaging behaviour
Meer, Yvonne van der - \ 2017
University. Promotor(en): Walter Gerrits, co-promotor(en): Alfons Jansman; Aart Lammers. - Wageningen : Wageningen University - ISBN 9789463431972 - 181
pigs - feeds - pig feeding - animal nutrition - amino acid metabolism - animal health - energy metabolism - abnormal behaviour - behaviour disorders - immune system - nutrition physiology - varkens - voer - varkensvoeding - diervoeding - aminozuurmetabolisme - diergezondheid - energiemetabolisme - abnormaal gedrag - gedragsstoornissen - immuunsysteem - voedingsfysiologie

It is economically and environmentally important to match the nutrient supply to the nutrient requirements in pig production. Until now, the effects of different sanitary conditions on energy and nutrient requirements are not implemented in recommendations for nutrient composition of pig diets. The current nutrient requirement data are based on studies with pigs in experimental settings, which can be regarded as rather optimal. Changes in nutrient requirements caused by differences in sanitary conditions are poorly documented. As in the pig production sector farm conditions are variable it is of major importance to determine the effects of low sanitary conditions (LSC) on requirements for amino acids and energy in growing pigs. Pigs under LSC have an increased risk of clinical and subclinical infections, resulting in a chronic stimulation of their immune system. Immune system stimulation is known to influence energy and amino acid metabolism. However, most studies in pigs evaluating the relationship between immune system stimulation and nutrient requirements often use specific experimental challenge models. Whereas such models have the obvious advantage of reproducibility and allow mechanistic insight in the effects of stimulating specific parts of the immune system, these models often induce clinical illness, rather than subclinical infections. Results obtained with such models may therefore be difficult to translate to practical situations. Therefore the objective of the present thesis was to study the effect of low and high sanitary conditions (HSC) on amino acids and energy metabolism in pigs. Also interactions between the immune system, nutrient metabolism and damaging behaviour of pigs were considered in this thesis.

The experiment described in Chapter 2 was designed to study the effect of different dietary crude protein levels and extra amino acid supplementation on the growth performance of pigs kept under different sanitary conditions. In a 2×2×2 factorial arrangement, 68 groups of 9 pigs were allocated to either LSC or HSC, and were offered ad libitum access to two different diets, a normal crude protein concentration diet or a low crude protein concentration diet, each having either a basal dietary amino acid profile or supplemented dietary amino acid profile containing 20% more methionine, threonine, and tryptophan compared with the basal profile. The pigs were followed from 10 weeks of age until slaughter. Haptoglobin concentrations in serum and IgG antibody titers against keyhole limpet heamocyanin, collected in the starter, grower, and finisher phases, and pleuritis scores at slaughter were greater for LSC pigs compared with HSC pigs, illustrating that sanitary conditions affected health conditions. The average daily gain and gain to feed ratio were greater for HSC pigs compared with LSC pigs. A 20% increase in dietary supplementation of methionine, threonine, and tryptophan relative to lysine increased gain to feed ratio more in LSC than in HSC pigs. The results therefore illustrated that dietary requirements for methionine. threonine, and tryptophan were greater for LSC compared with HSC pigs.

In Chapter 3 the damaging behaviour of 576 pigs from the experiment in Chapter 2 was evaluated. At 15, 18, and 24 weeks of age, prevalence of tail and ear damage, and of tail and ear wounds was scored. At 20 and 23 weeks of age, frequencies of biting behaviour and aggression were scored by behaviour sampling. The prevalence of ear damage during the finisher phase and the frequency of ear biting were increased in LSC compared with HSC pigs. The frequency of ear biting was increased in low protein fed pigs compared with normal protein fed pigs. The supplemented AA profile reduced ear biting only in LSC pigs. The prevalence of tail wounds was lower for pigs in LSC than for pigs in HSC in the grower phase. Regardless of dietary amino acid profile or sanitary status, pigs fed low protein diets showed more ear biting, tail biting, belly nosing, other oral manipulation directed at pen mates, and aggression than pigs fed normal protein diets, with no effect on ear or tail damage. In conclusion, both LSC and a reduction of dietary protein increased the occurrence of damaging behaviours in pigs and therefore may negatively impact pig welfare.

The experiment of Chapter 4 was designed to quantify the difference in energy requirements for maintenance, and in incremental efficiencies for deposition of dietary energy and protein in the body of clinically healthy pigs kept under LSC or HSC, fed a basal diet either or not supplemented with additional methionine, threonine and tryptophan.

In a 2 × 2 factorial arrangement, 24 groups of 6 pigs each were allocated to either a LSC or HSC, and were offered two different diets having either a basal or a dietary amino acid profile supplemented with methionine, threonine, and tryptophan. For each group of pigs, complete energy and nitrogen balances were determined during two consecutive weeks, during which feed was available ad libitum or at 70% of ad libitum. Fasting heat production was determined over a 25 h period of fasting after a period of restricted feeding. Low sanitary conditions increased fasting heat production from 696 to 750 kJ/(kg BW0.6 . d), regardless of the dietary amino acid supplementation. The incremental efficiency of ingested nitrogen for retention in the body was reduced in LSC pigs from 73 to 53%, but incremental efficiencies of digestible energy intake for fat deposition in the body were unaffected by the experimental treatments. These findings showed that the effects of continuous immune stimulation by introducing LSC, was affecting energy and nutrient efficiencies of pigs both at maintenance level and at a feeding level close to ad libitum intake.

In Chapter 5 diurnal patterns for heat production, respiratory quotient, and carbohydrate and fat oxidation of the pigs studied in the experiment of Chapter 4 were evaluated to get more insight in the mechanisms behind the effects found in Chapter 4. The LSC pigs had reduced activity compared with HSC and a higher resting metabolic rate during the period of restricted feeding, especially during the light parts of the day. Therefore the diurnal energy expenditure pattern of LSC and HSC pigs can be considered as different. Fat and carbohydrate oxidation patterns were not different for LSC and HSC pigs, indicating that protein and fat deposition during the day was similar for LSC and HSC pigs.

Overall, the results of this thesis indicate that both energy and AA requirements are greater in LSC pigs compared with HSC pigs. It is questionable, however, whether it is nutrient and cost effective and biologically possible to satisfy these increased nutrient requirements in LSC pigs, as the incremental efficiency of N for retained protein is low, and ADFI is reduced for LSC pigs compared with HSC pigs. The present thesis demonstrates that care should be taken in reducing dietary protein concentrations to improve protein efficiency in pigs, as it incurs a risk to increased damaging behaviours, particularly when pigs are kept under LSC.

Interactions and functionalities of the gut revealed by computational approaches
Benis, Nirupama - \ 2017
University. Promotor(en): Mari Smits; Vitor Martins dos Santos, co-promotor(en): Dirkjan Schokker; Maria Suarez Diez. - Wageningen : Wageningen University - ISBN 9789463434546 - 247
pigs - mice - digestive tract - digestive system - intestinal microorganisms - intestinal mucosa - computational science - immune system - feeds - animal nutrition - nutrition physiology - animal health - varkens - muizen - spijsverteringskanaal - spijsverteringsstelsel - darmmicro-organismen - darmslijmvlies - immuunsysteem - voer - diervoeding - voedingsfysiologie - diergezondheid

The gastrointestinal tract is subject of much research for its role in an organism’s health owing to its role as gatekeeper. The tissue acts as a barrier to keep out harmful substances like pathogens and toxins while absorbing nutrients that arise from the digestion of dietary components in in the lumen. There is a large population of microbiota that plays an important role in the functioning of the gut. All these sub-systems of the gastrointestinal tract contribute to the normal functioning of the gut. Due to its various functionalities, the gut is able to respond to different types of stimuli and bring the system back to homeostasis after perturbations.

The work done in this thesis uses several bioinformatic tools to improve our understanding of the functioning of the gut. This was achieved with data from model animals, mice and pigs which were subjected to changing environments before their gastrointestinal response was measured. Different types of stimuli were studied (eg, antibiotic exposure, changing diets and infection with pathogens) in order to understand the response of the gut to varying environments. This data was analysed using different data integration techniques that provide a holistic view of the gut response.

Vertical data integration techniques look for associations between different types of ~omics data to highlight possible interactions between the measured variables. Lateral integration techniques allow the study of one type of ~omics data over several time points or several experimental conditions. Using these techniques, we show proof of interactions between different sub-systems of the gut and the functional plasticity of the gut. Of the several hypotheses generated in this thesis we have validated several using existing literature and one using an in-vitro system. Further validation of these hypotheses will increase understanding of the responses of the gut and the interactions involved.

The aging immune system and nutritional interventions
Beek, Adriaan A. - \ 2017
University. Promotor(en): Huub Savelkoul; R.W. Hendriks, co-promotor(en): P.J.M. Leenen; Harry Wichers. - Wageningen : Wageningen University - ISBN 9789462579552 - 250
immune system - senescence - gastrointestinal microbiota - basophils - macrophages - dna - nutritional intervention - immuunsysteem - veroudering - microbiota van het spijsverteringskanaal - basofielen - macrofagen - maatregel op voedingsgebied

The increased numbers of elderly people pose a major burden to public health care and society. DNA damage is considered to be the major origin of age-related changes in the body. With aging, the immune system becomes deregulated and is characterized by a low-grade inflammation (inflammaging). In this thesis, we investigate the effects of nutritional and microbial interventions on the aging immune system.

In chapter 2, we elaborate on the role of basophils in the immune system, particularly in the initiation and perpetuation of allergic immune responses. We found that basophils and dendritic cells interact in vitro, which reciprocally affects their surface markers and cytokine production. Thus, by modulating cytokine production and surface marker expression on dendritic cells, basophils may act as accessory cells in immune responses. Because little is known about the effects of aging on basophils, we investigated in chapter 3 whether basophils are affected with aging. We found that frequencies of basophils in the spleen of aging mice are increasing, while their phenotype in bone marrow and spleen changes. Moreover, to investigate the role of microbiota in the aging process, we studied the effects of microbiota transfer from young or aged mice into germfree mice. Aging, and microbiota from aged mice, in particular affect differentiation and function of basophil precursors. These findings warrant further studies on the role of basophils in T helper-2 immune responses with aging.

The contribution of macrophages to inflammaging is described in chapter 4. Important aspects for macrophage polarization and function, like autophagy and cellular metabolism, are discussed. Targeting of aged macrophages by (nutritional) interventions may open up new therapeutic opportunities for elderly.

In chapter 5, we studied the in vitro interaction between bacterial supplementations and immune cells (whole spleen cells and macrophages). We noticed that aged immune cells mount a different response to bacterial strains than young immune cells. Based on these outcomes, we selected three bacterial strains (Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Bifidobacterium breve DSM20213) for in vivo application in chapter 6. We used Ercc1-/Δ7 mice, which lack fully functional ERCC1 protein. As a consequence, DNA repair is compromised, which results in accelerated aging features in all organs, including the immune system. We supplemented Ercc1-/Δ7 mice, as well as control Ercc1+/+ mice with the three selected bacterial strains. We observed that L. plantarum prevented the age-related decline in mucus barrier function of Ercc1-/Δ7 mice, whereas B. breve exacerbated the age-related decline in mucus barrier. L. casei supplementation elevated multiple systemic inflammatory markers in Ercc1-/Δ7 mice, including Ly6Chi monocytes, neutrophils, and Th17 cells in spleen. Strikingly, we found major changes in the mucus barrier and immune system after supplementation of Ercc1-/Δ7 mice with L. plantarum and L. casei, but not after supplementation of Ercc1+/+ mice. Therefore, we conclude that caution is needed in the selection of candidate probiotic strains for supplementation of aging individuals.

In chapter 7, we took a different approach to modulate the aging immune system by applying dietary tryptophan restriction in Ercc1+/+ and Ercc1-/Δ7 mice. We observed that in both mouse models dietary tryptophan restriction modulated B cell development and microbiota composition. In particular, we found a near-complete absence of B cell precursors in the bone marrow after dietary tryptophan restriction. The decline in B cell precursors was correlated with decreased abundance of the Akkermansia and Alistipes bacterial strains in the intestine. Thus, our results show that dietary tryptophan restriction is a powerful intervention to shape immunity and gut microbiota, also in aging. In chapter 8, we assessed the role of microbiota in the aging gut and immune system. Microbiota from young and aged mice were transferred to germfree mice. Aged microbiota induced higher T helper-1 cell and regulatory T cell frequencies in the spleen. In the ileum, the expression of inflammatory markers was increased after transferring aged microbiota, accompanied by differences in the abundance of microbial species. We conclude that senescent microbiota contribute to the inflammaging observed in aging mice.

In chapter 9, we discuss the findings presented in this thesis, concluding with directions for future research. In summary, our studies show that the aging gut and immune system of mice can be modulated by nutritional and/or microbial interventions. Interestingly, our mouse models clearly provide evidence that age-related effects could be reverted or prevented by these interventions. Nevertheless, our studies at the same time show the need for translational research in order to apply the presented dietary and microbial interventions in elderly.

Immuunsysteem sturen met voer
Have, H. ten; Smits, M.A. - \ 2015
V-focus 12 (2015)4. - ISSN 1574-1575 - p. 20 - 21.
varkens - varkenshouderij - diergezondheid - varkensvoeding - voedertoevoegingen - immuunsysteem - antigenen - darmen - pigs - pig farming - animal health - pig feeding - feed additives - immune system - antigens - intestines
Het onderzoeksprogramma Feed4Foodure werkt aan een meetlat om te voorspellen wat het vermogen is van een dier om adequaat te reageren als het wordt blootgesteld aan ziekteverwekkers. Dit wordt de immuuncompetentie van het dier genoemd. Deze immuuncompetentie is te beïnvloeden door onder andere diervoeding en voederadditieven, vertelt onderzoeker Mari Smits van Wageningen UR.
Antibiotica nadelig voor afweerontwikkeling jonge big
Leneman, M. ; Smits, M.A. - \ 2015
Veehouder en Veearts 29 (2015)3. - p. 6 - 8.
varkenshouderij - biggen - diergezondheid - antibiotica - immuunsysteem - diergeneeskunde - pig farming - piglets - animal health - antibiotics - immune system - veterinary science
Dat er vanwege resistentie ontwikkeling terughoudend met antibiotica moet worden omgesprongen is inmiddels gemeengoed. Wetenschappelijk onderzoek bij biggen op onderzoeksbedrijf Sterksel en bij Wageningen UR Livestock Research wijst nu ook uit dat antibiotica toediening in de eerste levensfase een langdurige negatieve invloed op de afweer heeft.
Herpesvirus kaapt afweersysteem karpers
Sikkema, A. ; Forlenza, M. - \ 2015
Resource: weekblad voor Wageningen UR 10 (2015)5. - ISSN 1874-3625 - p. 8 - 8.
herpes - karper - dierenvirussen - immuunsysteem - diergezondheid - cyprinidae - carp - animal viruses - immune system - animal health
Een dodelijk virus bouwde meer dan 400 miljoen jaar geleden een molecuul van het afweersysteem van vissen in zijn genoom, tonen Wageningse celbiologen voor het eerst aan. Daardoor kan dit koiherpesvirus de afweer van karpers en sierkarpers (koi) omzeilen.
Impact of health status on amino acid requirements of growing pigs : towards feeding strategies for farms differing in health status
Kampman-van de Hoek, E. - \ 2015
University. Promotor(en): Wouter Hendriks, co-promotor(en): Walter Gerrits; Alfons Jansman. - Wageningen : Wageningen University - ISBN 9789462573437 - 184
varkens - afmesten - diergezondheid - aminozuren - voedingsstoffenbehoeften - voedingseiwit - aminozuurmetabolisme - stikstofretentie - immuniteitsreactie - immuunsysteem - varkensvoeding - diervoeding - pigs - finishing - animal health - amino acids - nutrient requirements - dietary protein - amino acid metabolism - nitrogen retention - immune response - immune system - pig feeding - animal nutrition


There is large variation in the production performance of commercial growing-finishing pig farms. This variation even exists when pigs have a similar genetic background and fed similar diets. The health status is one of the major factors contributing to this large variation in pig performance, as activation of the immune system can decrease feed intake, body weight gain and increase nutrient utilisation for immune system functioning. As a consequence, amino acids (AA) are repartitioned from skeletal muscle deposition towards utilisation for immune system functioning. Current requirement estimates for growing-finishing pigs are formulated to maximize protein deposition for growth and do not take into account the increased utilization of AA for immune functioning as induced by health challenging conditions. This lack of knowledge hampers the ability of feed manufacturers to optimize diets and improve pig performance. The main objective of the present thesis was to quantify the effect of health status on AA requirements for body protein deposition and for immune system functioning of growing pigs.

A health status web was developed as a tool to categorize growing-finishing pig farms on the basis of their health status. The health status web can be of use for feed manufacturers to develop targeted strategies to accommodate the nutritional requirements of pigs belonging to particular groups of farms sharing a common health status. A dose-response technique was developed, which is a simple, accu­rate technique to quantitatively estimate changes in AA requirements of individual meal-fed pigs. Nevertheless, a minimum time period of 21 days is required for each individual, which makes the technique inappropriate for studying the effect of immune system activation on AA requirements. The combined measurements of whole body N retention, plasma irreversible loss rate (ILR, i.e. the amount of free AA that disappears per unit of time from the plasma pool for protein synthesis or oxidation), urea entry and appearance of 13C into plasma proteins, provided insight into the consequences of immune system activation on AA metabolism.

Pigs selected from a farm with a suboptimal health status had greater serum haptoglobin, lower serum albumin concentrations, and greater leukocyte counts in blood at the start of the experiment than pigs selected from a farm with a high health status, indicating a higher level of immune system activation. The occurrence of compensatory gain in pigs from a farm characterized as having a suboptimal health status proves, however, that it is difficult to maintain a contrast in health status, and that pigs can adapt quickly to a change in housing conditions. In the absence of effects on feed intake, health challenging conditions may affect performance due to alterations in post-absorptive AA metabolism, as also indicated by increased urinary N losses, and a tendency for a reduced N retention and a lower utilization of digestible N for N retention in pigs with a systemic inflammation, or by a reduction in faecal nutrient digestibility as indicated for dry matter and N in pigs from a farm with a suboptimal health status. The observed changes in protein and AA metabolism after immune stimulation imply that especially tryptophan may become limiting during immune system activation, whereas lysine becomes excessive. Furthermore, the utilization of methionine, tyrosine, and valine for immune system functioning seems to increase in pigs with a systemic lung inflammation. In addition, the dietary AA or protein supply was able to modulate the acute phase response pre- and post-challenge, stressing the importance of an adequate dietary AA supply for appropriate functioning of the immune system of growing-finishing pigs.

Before implementing targeted feeding strategies for farms sharing a common health status, future research should be conducted to study the possible beneficial effects of increasing the dietary supply of particularly tryptophan, methionine, tyrosine, and valine relative to lysine for immune system function and for body protein deposition in pigs from farms with a different health status.

Impact on gut development of an early life oral antibiotic intervention in broilers
Schokker, D. ; Jansman, A.J.M. ; Bruin, N. de; Vastenhouw, S.A. ; Bree, F.M. de; Rebel, J.M.J. ; Smits, M.A. - \ 2015
Wageningen : Wageningen UR Livestock Research (Livestock Research report 859) - 30
vleeskuikens - antibiotica - adequate immuniteit - immuunsysteem - darmmicro-organismen - microbiota van het spijsverteringskanaal - dierziektepreventie - diergezondheid - pluimveehouderij - broilers - antibiotics - immune competence - immune system - intestinal microorganisms - gastrointestinal microbiota - animal disease prevention - animal health - poultry farming
The current report describes an experiment that was conducted to investigate the effect of a shortterm antibiotic intervention in early life on microbial colonization and gut development in broilers. Such an intervention is expected to have negative effects on immune competence. This experiment was performed within the frame work of the Feed4Foodure program line “Nutrition, Intestinal Health, and Immunity” in combination with partners from Breed4Food.
The role of microbiota for a balanced immune system
Smits, M.A. ; Jansman, A.J.M. ; Savelkoul, H.F.J. ; Rebel, J.M.J. - \ 2014
Tijdschrift voor Diergeneeskunde 139 (2014)6. - ISSN 0040-7453 - p. 22 - 26.
microbiota van het spijsverteringskanaal - spijsverteringsstoornissen - maagdarmziekten - immuniteit - diergezondheid - immuunsysteem - gastrointestinal microbiota - digestive disorders - gastrointestinal diseases - immunity - animal health - immune system
Central Veterinary Institute, onderdeel van Wageningen UR. Wageningen UR Livestock Research en Wageningen Universiteit hebben hun expertise en onderzoek naar het functioneren van het maagdarmkanaal bij landbouwhuisdieren gebundeld en geïntensiveerd. Zij hebben dit gedaan omdat de processen die in het maagdarmkanaal plaatsvinden, niet alleen van belang zijn voor een efficiënte voervertering en benutting maar ook voor de afweer van landbouwhuisdieren tegen infectieziekten. In het kader van de genoemde samenwerking zijn expertises en onderzoekstechnieken bij elkaar gebracht waarmee complexe processen in het maagdarmkanaal beter kunnen worden ontrafeld.
Interview Professor Joost van Neerven over onderzoek naar vermindering van allergieën door gerichte voeding en aanvullende micronutriënten
Neerven, R.J.J. van - \ 2014
Wageningen : Wageningen UR
voeding en gezondheid - voedselonderzoek - immuunsysteem - ziektepreventie - infectieziekten - allergieën - gezondheidsbevordering - nutrition and health - food research - immune system - disease prevention - infectious diseases - allergies - health promotion
Met gerichte voeding en aanvullende micronutriënten kan de weerstand tegen infecties in de luchtwegen, tegen allergieën, en tegen ontstekingen worden vergroot. Dat is van groot belang voor kinderen onder de 5 jaar en voor 65-plussers, die het vaakst door deze aandoeningen worden geplaagd. De weerstand in weefsels die bedekt zijn met een slijmvlies in het gebied van de mond, keel, en neus is nog nauwelijks onderzocht. Toch kan dit onderzoek veel opleveren, vindt prof. Joost van Neerven.
Mucosal immunity : barriers, bugs, and balance
Neerven, R.J.J. van - \ 2014
Wageningen : Wageningen University, Wageningen UR - ISBN 9789462571952 - 24
immuniteit - immuniteitsreactie - immuunsysteem - immunologie - infectieziekten - ontsteking - orale vaccinatie - voeding - immunity - immune response - immune system - immunology - infectious diseases - inflammation - oral vaccination - nutrition
Nutritional intervention in animals: benchmarking of strategies, monitoring biomarkers and immune competence
Krimpen, M.M. van; Hulst, M.M. ; Meulen, J. van der; Schokker, D. ; Savelkoul, H.F.J. ; Tijhaar, E.J. ; Rutten, V.P.M.G. - \ 2014
Wageningen : Wageningen UR Livestock Research (Livestock Research report 800) - 116
maatregel op voedingsgebied - biomarkers - adequate immuniteit - vee - diergezondheid - immuunsysteem - biologische processen - veehouderij - voeding en gezondheid - diervoedering - dierenwelzijn - nutritional intervention - immune competence - livestock - animal health - immune system - biological processes - livestock farming - nutrition and health - animal feeding - animal welfare
The current study covers a review of literature regarding a number of topics related to immune competence in farm animals, which are introduced in chapter 1. These topics are: 1) A demonstration of the relationship between functional feed components and the expression of genes/biological processes that are involved in gut health of farm animals; 2) A description of available models, that can be used to investigate the effects of nutritional interventions on immune related parameters in animals; 3) A review of the effects of nutritional interventions in the maternal, neonatal and post-neonatal phase on the development of the innate and acquired immune system; 4) A review of the relationship between the immune system in the gut and in the upper airways, whereas the question will be addressed how the immune system in the upper airways can be affected by nutritional interventions.
Fungal plant pathogens and the plant immune system
Wit, P.J.G.M. de - \ 2014
Wageningen : Wageningen University, Wageningen UR - ISBN 9789461739766 - 48
plantenziekteverwekkende schimmels - planten - verdedigingsmechanismen - immuunsysteem - openbare redes - plant pathogenic fungi - plants - defence mechanisms - immune system - public speeches
Fungi are notorious plant pathogens and continuously threat global food production. In the last decades we have obtained a better understanding of infection strategies of fungi and the plant immune system. This has facilitated more efficient introduction of disease resistance genes in crop plants by plant breeders. A brief overview of progress in research and applications will be provided as well as a glimpse into the future.
'Je moeder leert je wie je vijanden zijn'
Makkink, C. ; Parmentier, H.K. - \ 2014
De Molenaar 2014 (2014)7. - ISSN 0165-4284 - p. 26 - 27.
vleeskuikenouderdieren - immuunsysteem - immuniteitsreactie - epigenetica - diervoeding - broiler breeders - immune system - immune response - epigenetics - animal nutrition
Via de voeding van ouderdieren kan de werking van het immuunsysteem van de nakomelingen worden beïnvloed. Het is een uitdaging om interventies te vinden die het immuunsysteem van landbouwhuisdieren optimaliseren, zo luidde de conclusie tijdens de Feed4Foodure-themamiddag.
1Health4Food : focus op gezondheid mens-dier
Kimman, T.G. ; Mevius, D.J. ; Antonis, A.F.G. ; Parée, P. - \ 2014
V-focus 2014 (2014)1. - ISSN 1574-1575 - p. 22 - 24.
veehouderij - dierlijke productie - diergezondheid - volksgezondheid - wetenschappelijk onderzoek - onderzoeksprojecten - diagnostiek - antibioticaresistentie - volksgezondheidsbevordering - verbreed spectrum bèta-lactamases - immuniteit - immuunsysteem - immunologie - voedselveiligheid - voeding en gezondheid - mens-dier relaties - livestock farming - animal production - animal health - public health - scientific research - research projects - diagnostics - antibiotic resistance - sanitation - extended spectrum beta-lactamases - immunity - immune system - immunology - food safety - nutrition and health - human-animal relationships
1Health4Food is een ambitieus onderzoeksprogramma op het gebied van dier- en volksgezondheid. Het landbouwbedrijfsleven heeft in sterke mate bepaald waar de prioriteiten moeten liggen: bij de ESBL’s en de snelle diagnostiek. Binnen 1Health4Food wordt kennis ontwikkeld voor meerdere sectoren, kennis die veehouders en hun adviseurs, zoals dierenartsen, in staat stellen om rendabel te produceren op een wijze die ook veilig is voor de mens. De ambitie is om in de toekomst gezamenlijk een gezonde en veilige veehouderij te realiseren.
Stimulation of the innate immune system of carp: role of Toll-like receptors
Pietretti, D. - \ 2013
University. Promotor(en): Geert Wiegertjes; Huub Savelkoul, co-promotor(en): Maria Forlenza. - Wageningen : Wageningen University - ISBN 9789461737878 - 213
karper - cyprinus - immuunsysteem - verdedigingsmechanismen - immuniteitsreactie - immunostimulatie - bèta-glucaan - macrofagen - receptoren - immunologie - visteelt - aquacultuur - carp - immune system - defence mechanisms - immune response - immunostimulation - beta-glucan - macrophages - receptors - immunology - fish culture - aquaculture

Toll-like receptors (TLRs), named after the Toll gene identified in fruit flies, are a family of evolutionary conserved proteins that play a key role in the innate immune system. TLRs are found inside or on the surface of immune cells of virtually all-living animals and recognize integral parts of microbes. Thereby, they are excellent candidate receptors for controlled stimulation of the innate immune system of, for example, fish in aquaculture. β-glucans are microbial compounds routinely added to fish feed for their health-promoting effects. They regulate innate immunity by stimulating fish cells to produce more oxygen and nitrogen radicals but are not recognized by TLRs.Instead, TLRs of cyprinid fish (zebrafish, carp) are stimulated by viral and/or parasitic infection. Although immunostimulation by β-glucans occurs via yet undefined receptors certainly, addition of integral but harmless parts of microbes to fish feed may help controlfish diseases in aquaculture.

RegIII proteins as gatekeepers of the intestinal epithelium
Loonen, L.M.P. - \ 2013
University. Promotor(en): Jerry Wells, co-promotor(en): Peter van Baarlen. - S.l. : s.n. - ISBN 9789461736727 - 205
eiwitten - darmen - darmslijmvlies - darmziekten - colitis - bacterieziekten - immuunsysteem - verdedigingsmechanismen - muizen - diermodellen - microbiologie - immuniteit - geneeskunde - proteins - intestines - intestinal mucosa - intestinal diseases - bacterial diseases - immune system - defence mechanisms - mice - animal models - microbiology - immunity - medicine

Mammalian RegIII proteins are expressed in the intestine and in the pancreas in response to inflammation or infection. In the mouse intestine, expression of RegIIIβ and RegIIIγ is increased by microbial colonization, inflammation and infection. At the outset of this thesis human PAP and mouse RegIIIγ were reported to be bactericidal for Gram-positive bacteria. Additionally, human PAP had been shown to attenuate NF-κbsignallingin human monocytes and epithelial cells and administration of anti-PAP antibodies increased inflammation in an experimental rat model of acute pancreatitis. The overarching goals of this thesis were to find out more about the protective role of mouse RegIIIβ and RegIIIγ in the intestine and explore their protective role in colitis and bacterial infection.

In Chapter 2 we investigated expression of RegIIIβ and RegIIIγ in intestine of Muc2 knockout (-/-) mice, which develop colitis after about 4 weeks, due to the absence of a secreted mucus layer in the small intestine or colon. RegIII proteins were expressed in Paneth cells, enterocytes and goblet cells pointing to a new function for goblet cells in innate immunity. Ang4 expression was confined to Paneth cells and goblet cells. Absence of Muc2 increased expression levels of RegIIIβ, RegIIIγ, and Ang4 and colitis appeared first in the distal colon where the RegIII expression is lowest.

In Chapter 3 we investigated the distinct phases of colitis development in Muc2-/- mice from before weaning to 4 and 8 weeks of age, also taking into account the effect that mucin deficiency has in the ileum. Gene set enrichment approaches showed increased expression of innate and adaptive immune pathways associated with colitis over time, whereas in the ileum many immune signalling pathways were down-regulated. Nevertheless, RegIIIβ and RegIIIγ were significantly upregulated, suggesting their proposed antimicrobial and/or anti-inflammatory activities might be related to the suppression of immune pathways and avoidance of immune-mediated damage. Furthermore, we showed that RegIIIβ could specifically bind to mucin and fucosylated glycans in vitro, which may serve to inhibit bacterial binding to membrane bound mucins on the epithelium, and also enable RegIIIβ to be retained in the secreted mucin.

An in vitro approach was used in Chapter 4, where we investigated the activities of RegIIIγ and RegIIIβby expressing and purifying recombinant proteins. Both proteins were insoluble when expressed in E. coli but RegIIIβ could be expressed and secreted in baculovirus as a soluble protein. As previous work reported that RegIII proteins were bactericidal even when produced as inclusion bodies in E. coli and refolded, we followed similar procedures to obtain soluble RegIII proteins. In our hands both the E. coli and baculovirus produced proteins bound strongly to both Gram-positive and Gram-negative bacteria after processing of an N-terminal pro-peptide by trypsin, but lacked any appreciable bactericidal activity. Furthermore these proteins did not influence the growth of Salmonella enteritidis andListeria monocytogenes. Attempts to crystallize the proteins were unsuccessful but structural models of the protein were generated based on the crystal structure of human PAP. These models were used to dock known ligands of RegIIIγ or RegIIIβ. Only one ligand is known for RegIIIγ, which is peptidoglycan, but for RegIIIβ the ligands include peptidoglycan, lipid A and the fucose-containing glycans identified in chapter 3. RegIIIβ was predicted to have two different binding sites which would allow it to bind to mucins and bacteria simultaneously, thereby preventing penetrating of the mucus.

In Chapter 5 a RegIIIβ-/- mouse was used to study the role of the protein during infection with Gram-negative Salmonella enteritidis or Gram-positive Listeria monocytogenes. Whereas recovery of S. enteritidis orL. monocytogenes from faeces was similar in RegIIIβ-/- and wild type (WT) mice, significantly higher numbers of viable S. enteritidis, but not L. monocytogenes, were recovered from the colon, mesenteric lymph nodes, spleen, and liver of the RegIIIβ-/- than the WT mice. The results suggest that mouse RegIIIβ plays a protective role against intestinal translocation of the Gram-negative bacterium S. enteritidis but not against the Gram-positive bacterium L. monocytogenes.

In Chapter 6, the generation of a RegIIIγ-/- mouse is described. One of the main phenotypic differences between the RegIIIγ-/- and WT was an altered distribution of the ileal mucus and increased bacterial contact with the epithelium. Additionally, measurement of innate immune markers in the mucosa suggested heightened inflammation in the RegIIIγ-/- mice. Compared to WT mice, RegIIIγ-/- mice infected with S. enteritidis and L. monocytogenes showed an increase of mucosal inflammatory markers indicating protective, anti-microbial roles of RegIIIγ in defense against both Gram-positive and Gram-negative bacteria.

Chapter 7summarizes and discusses the key results of the thesis in the context of the wider literature and possible directions for future research

Immuunmodulatie door voeding "Van black box naar toolbox"
Wolthuis, A. ; Wichers, H.J. - \ 2013
Immuun 2 (2013)2. - p. 30 - 31.
voeding en gezondheid - immuunsysteem - immuniteit - gezondheidsbevordering - modulatie - immunomodulatoren - bèta-glucaan - voedingsvezels - nutrition and health - immune system - immunity - health promotion - modulation - immunomodulators - beta-glucan - dietary fibres
Prof. dr. Harry Wichers van Wageningen University & Research Centre doet onderzoek naar hoe voeding ons immuunsysteem een oppepper kan geven. "We kijken standaard naar medicijnen wanneer het er om gaat onze gezondheid te verbeteren. De mogelijkheden en het belang van voeding worden onderschat."
Nieuwe methoden voor risico- en gezondheidsanalyse producten : Efficient en relatief goedkoop
Mes, J.J. ; Meer, I. van der; Vos, R. de; Meulen, J. van der; Hulst, M.M. ; Smits, M.A. ; Hendriksen, P.J.M. ; Bovee, T.F.H. - \ 2013
Voeding Nu 15 (2013)3/4. - ISSN 1389-7608 - p. 24 - 26.
voedselanalyse - voedselveiligheid - analytische methoden - voeding en gezondheid - voedingsstoffen - spijsverteringsstelsel - immuunsysteem - food analysis - food safety - analytical methods - nutrition and health - nutrients - digestive system - immune system
Veel gezondheids- en veiligheidsonderzoek vindt plaats naar de afzonderlijke stoffen die in voeding voorkomen. Zo richt het gezondheidsonderzoek zich op het meten van de gehalten aan bioactieve vitamines, mineralen en (secundaire) metabolieten en het veiligheidsonderzoek op de contaminanten in voeding, zoals dioxines, residuen van behandelingsmiddelen en mycotoxinen. Onze voeding is echter geen mengsel van stoffen in een neutrale omgeving, maar een complexe matrix waarin stoffen met elkaar interacteren. Door de bioactieve effecten van het hele product centraal te zetten, kunnen de werkelijke effecten van voeding beter worden voorspeld.
On the modulation of innate immunity by plant-parasitic cyst nematodes
Postma, W.J. - \ 2013
University. Promotor(en): Jaap Bakker, co-promotor(en): Geert Smant; Aska Goverse. - S.l. : s.n. - ISBN 9789461735560 - 154
plantenparasitaire nematoden - globodera rostochiensis - heterodera schachtii - planten - interacties - immuniteit - immuunsysteem - modulatie - receptoren - signaaltransductie - moleculaire plantenziektekunde - plant parasitic nematodes - plants - interactions - immunity - immune system - modulation - receptors - signal transduction - molecular plant pathology

Plant-parasitic cyst nematodes are major agricultural pests worldwide. These obligate endoparasites invade the roots of host plants where they transform cells near the vascular cylinder into a permanent feeding site. Plants possess a multilayered innate immune system consisting of different types of extracellular and intracellular immune receptors. These enable detection of most invading nematodes and initiate immune responses that result in resistance. Many plant pathogens use effectors to overcome resistance. Here, modulation of plant innate immunity by plant-parasitic cyst nematodes was investigated. Extracellular immune receptor signaling and hormone-mediated signaling pathways were found to contain infection of susceptible Arabidopsis thalianawith Heterodera schachtii. A large family of effectors was identified in Globodera rostochiensis. One of these so-called SPRYSECs interacted with a novel CC-NB-LRR type resistance protein of a susceptible tomato without inducing resistance responses. Instead, the effector was found to suppress defense-related programmed cell death and resistance mediated by several CC-NB-LRR type resistance proteins. In addition, a secreted antimicrobial peptide was identified in G. rostochiensis. Plant-parasitic cyst nematodes thus most likely secrete effectors that protect against plant immune responses and secondary infections. The current evidence for the existence of immune modulating effectors is reviewed and directions for further research are given.

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