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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Invasive behavior of Campylobacter jejuni in immunosuppressed chicken
Vaezirad, Mahdi M. ; Keestra-Gounder, A.M. ; Zoete, Marcel R. de; Koene, Miriam G. ; Wagenaar, Jaap A. ; Putten, Jos P.M. van - \ 2017
Virulence 8 (2017)3. - ISSN 2150-5594 - p. 248 - 260.
Campylobacter - chicken - colonization - glucocorticoids - innate immunity - invasion - Toll-like receptor
Campylobacter jejuni is a predominant cause of gastroenteritis in humans but rather harmless in chickens. The basis of this difference is unknown. We investigated the effect of the chicken immune defense on the behavior of C. jejuni using glucocorticoid (GC)-treated and mock-treated 17-day old Ross 308 chicken bearing in mind that GCs have immunosuppressive effects and dampen the innate immune response. The effect of GC administration on the behavior of C. jejuni was compared with that on infection with Salmonella Enteritidis to address possible microbe-associated differences. Our results revealed that GC treatment fastened the intestinal colonization of C. jejuni (p <0.001) and enhanced its dissemination to the liver (p = 0.007). The effect of GC on intestinal colonization of S. Enteritidis was less pronounced (p = 0.033) but GC did speed up the spread of this pathogen to the liver (p <0.001). Cytokine transcript analysis showed an up to 30-fold reduction in baseline levels of IL-8 mRNA in the cecal (but not spleen) tissue at Day 1 after GC treatment (p <0.005). Challenge with C. jejuni strongly increased intestinal IL-8, IL-6, and iNOS transcript levels in the non-GC treated animals but not in the GC-treated birds (P <0.005). In vitro assays with chicken macrophages showed that GC dampened the TLR agonist- and C. jejuni induced-inflammatory gene transcription and production of nitric oxide (P <0.005). Together, the results support the hypothesis that C. jejuni has the intrinsic ability to invade chicken tissue and that an effective innate immune response may limit its invasive behavior.
Recognition of coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors
Ammerdorffer, Anne ; Schoffelen, Teske ; Gresnigt, Mark S. ; Oosting, Marije ; Brok, Martijn H. Den; Abdollahi-Roodsaz, Shahla ; Kanneganti, Thirumala Devi ; Jong, Dirk J. De; Deuren, Marcel Van; Roest, Hendrik Jan ; Rebel, Johanna M.J. ; Netea, Mihai G. ; Joosten, Leo A.B. ; Sprong, Tom - \ 2015
The Journal of Infectious Diseases 211 (2015)6. - ISSN 0022-1899 - p. 978 - 987.
Coxiella burnetii - innate immunity - NOD-like receptors - pattern recognition - Q fever - singlenucleotide polymorphism - Toll-like receptors

Background. Infection with Coxiella burnetii can lead to acute and chronic Q fever. Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR6, nucleotide-binding oligomerization domain receptor 1 (NOD1), NOD2, and the mitogen-activated protein kinases are central in the innate immune response against microorganisms, but little is known about their role in the recognition of C. burnetii in humans. Methods. Human peripheral blood mononuclear cells (PBMCs) were stimulated with C. burnetii Nine Mile and the Dutch outbreak isolate C. burnetii 3262. TLRs were inhibited using specific antibodies or antagonists. Additionally, the influence of human polymorphisms in TLRs and Nod-like receptors (NLRs) on C. burnetii-induced cytokine production was assessed. Results. Inhibition of TLR2, p38, JNK, and ERK led to decreased cytokine responses in C. burnetii-stimulated human PBMCs. Humans with polymorphisms in TLR1 and NOD2 had reduced cytokine production, compared with humans with wild-type genotypes, after stimulation. Interestingly, polymorphisms in TLR6 led to decreased cytokine production after C. burnetii 3262 stimulation but not after C. burnetii Nine Mile stimulation. Conclusions. The TLR1/TLR2 heterodimer and NOD2 are important recognition receptors for the induction of cytokine responses against C. burnetii in humans. Furthermore, an interesting finding was the divergent recognition of C. burnetii Nine Mile and C. burnetii 3262.

Understanding plant immunity as a surveillance system to detect invasion
Cook III, D.E. ; Mesarich, C.H. ; Thomma, B.P.H.J. - \ 2015
Annual Review of Phytopathology 53 (2015). - ISSN 0066-4286 - p. 541 - 563.
disease-resistance gene - bacterial elicitor flagellin - syringae effectors avrb - host-selective toxins - innate immunity - arabidopsis-thaliana - molecular-patterns - microbe interactions - durable resistance - necrotrophic pathogens
Various conceptual models to describe the plant immune system have been presented. The most recent paradigm to gain wide acceptance in the field is often referred to as the zigzag model, which reconciles the previously formulated gene-for-gene hypothesis with the recognition of general elicitors in a single model. This review focuses on the limitations of the current paradigm of molecular plant-microbe interactions and how it too narrowly defines the plant immune system. As such, we discuss an alternative view of plant innate immunity as a system that evolves to detect invasion. This view accommodates the range from mutualistic to parasitic symbioses that plants form with diverse organisms, as well as the spectrum of ligands that the plant immune system perceives. Finally, how this view can contribute to the current practice of resistance breeding is discussed.
The battle for chitin recognition in plant-microbe interactions
Sánchez-Vallet, A. ; Mesters, J.R. ; Thomma, B.P.H.J. - \ 2015
FEMS Microbiology Reviews 39 (2015)2. - ISSN 0168-6445 - p. 171 - 183.
receptor-like kinase - medicago-truncatula roots - bacillus-circulans wl-12 - high-affinity binding - fungal cell-wall - nod factor - fusarium-oxysporum - botrytis-cinerea - innate immunity - aspergillus-nidulans
Fungal cell walls play dynamic functions in interaction of fungi with their surroundings. In pathogenic fungi, the cell wall is the first structure to make physical contact with host cells. An important structural component of fungal cell walls is chitin, a well-known elicitor of immune responses in plants. Research into chitin perception has sparked since the chitin receptor from rice was cloned nearly a decade ago. Considering the widespread nature of chitin perception in plants, pathogens evidently evolved strategies to overcome detection, including alterations in the composition of cell walls, modification of their carbohydrate chains and secretion of effectors to provide cell wall protection or target host immune responses. Also non-pathogenic fungi contain chitin in their cell walls and are recipients of immune responses. Intriguingly, various mutualists employ chitin-derived signaling molecules to prepare their hosts for the mutualistic relationship. Research on the various types of interactions has revealed different molecular components that play crucial roles and, moreover, that various chitin-binding proteins contain dissimilar chitin-binding domains across species that differ in affinity and specificity. Considering the various strategies from microbes and hosts focused on chitin recognition, it is evident that this carbohydrate plays a central role in plant–fungus interactions.
Immune activation mediated by the late blight resistance protein R1 requires nuclear localization of R1 and AVR1
Du, Y. ; Berg, J. ; Govers, F. ; Bouwmeester, K. - \ 2015
New Phytologist 207 (2015)3. - ISSN 0028-646X - p. 735 - 747.
disease-resistance - phytophthora-infestans - arabidopsis-thaliana - innate immunity - plant immunity - receptor - recognition - potato - gene - component
Resistance against oomycete pathogens is mainly governed by intracellular nucleotide-binding leucine-rich repeat (NLR) receptors that recognize matching avirulence (AVR) proteins from the pathogen, RXLR effectors that are delivered inside host cells. Detailed molecular understanding of how and where NLR proteins and RXLR effectors interact is essential to inform the deployment of durable resistance (R) genes. Fluorescent tags, nuclear localization signals (NLSs) and nuclear export signals (NESs) were exploited to determine the subcellular localization of the potato late blight protein R1 and the Phytophthora infestans RXLR effector AVR1, and to target these proteins to the nucleus or cytoplasm. Microscopic imaging revealed that both R1 and AVR1 occurred in the nucleus and cytoplasm, and were in close proximity. Transient expression of NLS- or NES-tagged R1 and AVR1 in Nicotiana benthamiana showed that activation of the R1-mediated hypersensitive response and resistance required localization of the R1/AVR1 pair in the nucleus. However, AVR1-mediated suppression of cell death in the absence of R1 was dependent on localization of AVR1 in the cytoplasm. Balanced nucleocytoplasmic partitioning of AVR1 seems to be a prerequisite. Our results show that R1-mediated immunity is activated inside the nucleus with AVR1 in close proximity and suggest that nucleocytoplasmic transport of R1 and AVR1 is tightly regulated.
Molecular and functional characterization of the scavenger receptor CD36 in zebrafish and common carp
Fink, I.R. ; Benard, E.L. ; Hermsen, G.J. ; Meijer, A.H. ; Forlenza, M. ; Wiegertjes, G. - \ 2015
Molecular Immunology 63 (2015)2. - ISSN 0161-5890 - p. 381 - 393.
toll-like receptors - salmon salmo-salar - cyprinus-carpio - density-lipoprotein - neutrophilic granulocytes - monoclonal-antibodies - accessory molecules - innate immunity - gene family - in-vivo
CD36 is a scavenger receptor which has been studied closely in mammals where it is expressed by many different cell types and plays a role in highly diverse processes, both homeostatic and pathologic. It is among other things important in the innate immune system, in angiogenesis, and in clearance of apoptotic cells, and it is also involved in lipid metabolism and atherosclerosis. Recently, in the cephalochordate amphioxus a primitive CD36 family member was described, which was present before the divergence of CD36 from other scavenger receptor B family members, SCARB1 and SCARB2. Not much is known on the Cd36 molecule in teleost fish. We therefore studied Cd36 in both zebrafish and common carp, two closely related cyprinid fish species. Whereas a single cd36 gene is present in zebrafish, carp has two cd36 genes, and all show conserved synteny compared to mammalian CD36. The gene expression of carp cd36 is high in brain, ovary and testis but absent in immune organs. Although in mammals CD36 expression in erythrocytes, monocytes and macrophages is high, gene expression studies in leukocyte subtypes of adult carp and zebrafish larvae, including thrombocytes and macrophages provided no indication for any substantial expression of cd36 in immune cell types. Surprisingly, analysis of the cd36 promoter region does show the presence of several binding sites for transcription factors known to regulate immune responses. Overexpression of carp cd36 locates the receptor on the cell surface of mammalian cell lines consistent with the predicted topology of cyprinid Cd36 with a large extracellular domain, two transmembrane domains, and short cytoplasmic tails at both ends. Gene expression of cd36 is down-regulated during infection of zebrafish with Mycobacterium marinum, whereas knockdown of cd36 in zebrafish larvae led to higher bacterial burden upon such infection. We discuss the putative role for Cd36 in immune responses of fish in the context of other members of the scavenger receptor class B family.
Activation of the chicken type I IFN response by infectious bronchitis coronavirus
Kint, J. ; Fernandez Gutierrez, M.M. ; Maier, H.J. ; Britton, P. ; Langereis, M.A. ; Koumans, J. ; Wiegertjes, G.F. ; Forlenza, M. - \ 2015
Journal of Virology 89 (2015)2. - ISSN 0022-538X - p. 1156 - 1167.
mouse hepatitis-virus - singly labeled probes - double-stranded-rna - rig-i - murine coronavirus - innate immunity - receptor activation - viral-rna - cells - induction
Coronaviruses from both the Alpha and Betacoronavirus genera, interfere with the type I interferon (IFN) response in various ways, ensuring limited activation of the IFN response in most cell types. Of Gammacoronaviruses that mainly infect birds, little is known about activation of the host immune response. We show that the prototypical Gammacoronavirus, infectious bronchitis virus (IBV), induces a delayed activation of the IFN response in primary renal cells, tracheal epithelial cells and in a chicken cell line. Ifnß expression in fact, is delayed with respect to the peak of viral replication and accompanying accumulation of dsRNA. In addition, we demonstrate that MDA5 is the primary sensor for Gammacoronavirus infections in chicken cells. Furthermore, we provide evidence that accessory proteins 3a and 3b of IBV modulate the IFN response at the transcriptional and translational level. Finally, we show that, despite the lack of activation of the IFN response during the early phase of IBV infection, signalling of non-self dsRNA through both MDA5 and TLR3 remains intact in IBV-infected cells. Taken together, this study provides the first comprehensive analysis of host-virus interactions of a Gammacoronavirus with avian innate immune responses.
How Specific is Non-Hypersensitive Host and Nonhost Resistance of Barley to Rust and Mildew Fungi?
Niks, R.E. - \ 2014
Journal of Integrative Agriculture 13 (2014)2. - ISSN 2095-3119 - p. 244 - 254.
quantitative trait loci - near-isogenic lines - powdery mildew - innate immunity - establishing compatibility - disease resistance - biotrophic fungi - puccinia-hordei - iii effector - cowpea rust
Full nonhost resistance can be defined as immunity, displayed by an entire plant species against all genotypes of a plant pathogen. Interesting biological questions are, whether the genes responsible for the nonhost status of a plant species have a general or a specific effectiveness to heterologous (“nonhost”) pathogens? Is the nonhost resistance to pathogens of plant species that are related to the nonhost based on R-genes or on other types of genes? We study this question in barley (Hordeum vulgare L.), which is a near-nonhost to several rusts (Puccinia) of cereals and grasses. By crosses and selection we accumulated susceptibility and developed an experimental line, SusPtrit, with high susceptibility to at least nine different heterologous rust taxa such as the wheat and Agropyron leaf rusts (P. triticina and P. persistens, respectively). At the microscopic level there is also some variation among barley accessions in the degree that the heterologous wheat powdery mildew (Blumeria graminis f.sp. tritici) is able to form haustoria in epidermal cells. So, also the genetics of the variation in level of nonhost resistance to heterologous mildew fungi can be studied in barley. Our data obtained on mapping populations involving three regular nonhost-immune accessions (Vada, Cebada Capa and Golden Promise) suggest that nonhost resistance is the joined effect of multiple, quantitative genes (QTLs) and very occasionally a major gene (R-gene?) is involved. Most QTLs have effect to only one or two heterologous rusts, but some have a wider spectrum. This was confirmed in a set of QTL-NILs. Those QTL-NILs are used to fine-map the effective genes. In some cases, a QTL region with effectiveness to several heterologous rusts might be a cluster of genes with a more narrow spectrum of effectiveness. Our evidence suggests that nonhost resistance in barley to rust and powdery mildew fungi of related Gramineae is not due to R-genes, but to pathogen species-specific quantitative resistance genes.
The Salivary Scavenger and Agglutinin in Early Life: Diverse Roles in Amniotic Fluid and in the Infant Intestine
Reichhardt, M.P. ; Jarva, H. ; Been, M. de; Rodriguez, J.M. ; Quintana, E.J. ; Loimaranta, V. ; Vos, W.M. de; Meri, S. - \ 2014
The Journal of Immunology 193 (2014)10. - ISSN 0022-1767 - p. 5240 - 5248.
surfactant protein-d - secretory immunoglobulin-a - malignant brain-tumors - terminal differentiation - bacterial recognition - streptococcus-mutans - glycoprotein gp-340 - epithelial-cells - innate immunity - receptor
The salivary scavenger and agglutinin (SALSA), also known as gp340 and dmbt1, is an antimicrobial and inflammation-regulating molecule located at the mucosal surfaces. The present study revealed that SALSA was present in the amniotic fluid (AF) and exceptionally enriched in both meconium and feces of infants. Based on immunological and mass spectrometric analysis, SALSA was estimated to constitute up to 4–10% of the total protein amount in meconium, making it one of the most abundant proteins. SALSA proteins in the AF and intestinal samples were polymorphic and exhibited varying polypeptide compositions. In particular, a different abundance of peptides corresponding to functionally important structures was found in the AF and intestinal SALSA. The AF form of SALSA had a more intact structure and contained peptides from the zona pellucida domain, which is involved in cell differentiation and oligomerization. In contrast, the intestinal SALSA was more enriched with the scavenger receptor cysteine-rich domains. The AF, but not the meconium SALSA, bound to Streptococcus pyogenes, S. agalactiae, S. gordonii, and Escherichia coli. Furthermore, differential binding was observed also to known endogenous ligands C1q, mannose-binding lectin, and secretory IgA. Our results have thus identified mucosal body compartments, where SALSA is particularly abundant, and suggest that SALSA exhibits varying functions in the different mucosal locations. The high levels of SALSA in AF and the infant intestine suggest a robust and important function for SALSA during the fetal development and in the mucosal innate immune defense of infants.
IL-37 protects against obesity-induced inflammation and insulin resistance
Ballak, D.B. ; Diepen, J.A. van; Moschen, A.R. ; Jansen, H. ; Hijmans, A. ; Groenhof, G.J. ; Leenders, F. ; Bufler, P. ; Boekschoten, M.V. - \ 2014
Nature Communications 5 (2014). - ISSN 2041-1723 - 12 p.
white adipose-tissue - high-fat diet - human interleukin-1-alpha - innate immunity - beta-cells - mice - receptor - family - expression - members
Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member ¿IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human ¿IL-37 (¿IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of ¿adiponectin and preserved ¿glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant ¿IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state ¿IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal ¿IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that ¿IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.
Phenotypic analyses of Arabidopsis T-DNA insertion lines and expression profiling reveal that multiple L-type lectin receptor kinases are involved in plant immunity
Wang, Y. ; Bouwmeester, K. ; Beseh, P. ; Shan, W. ; Govers, F. - \ 2014
Molecular Plant-Microbe Interactions 27 (2014)12. - ISSN 0894-0282 - p. 1390 - 1402.
pattern-triggered immunity - phytophthora-infestans - salicylic-acid - defense responses - innate immunity - thaliana - gene - resistance - biology - roles
L-type lectin receptor kinases (LecRKs) are membrane-spanning receptor-like kinases with putative roles in biotic and abiotic stress responses and in plant development. In Arabidopsis, 45 LecRKs were identified but their functions are largely unknown. Here, a systematic functional analysis was carried out by evaluating phenotypic changes of Arabidopsis LecRK T-DNA insertion lines in plant development and upon exposure to various external stimuli. None of the LecRK T-DNA insertion lines showed clear developmental changes, neither under normal conditions nor upon abiotic stress treatment. However, many of the T-DNA insertion lines showed altered resistance to Phytophthora brassicae, Phytophthora capsici, Pseudomonas syringae or Alternaria brassicicola. One mutant defective in LecRK-V.5 expression, was compromised in resistance to two Phytophthora spp. but showed enhanced resistance to P. syringae. LecRK-V.5 overexpression confirmed its dual role in resistance and susceptibility depending on the pathogen. Combined analysis of these phenotypic data and LecRK expression profiles retrieved from public datasets revealed that LecRKs which are hardly induced upon infection or even suppressed are also involved in pathogen resistance. Computed co-expression analysis revealed that LecRKs with similar function displayed diverse expression patterns. Since LecRKs are widespread in plants, the results presented here provide invaluable information for exploring the potential of LecRKs as novel sources of resistance in crops.
Functional analysis of the tomato immune receptor Ve1 through domain swaps with Its non-functional homolog Ve2
Fradin, E.F. ; Zhang, Z. ; Rövenich, H. ; Song, Y. ; Liebrand, T.W.H. ; Masini, L. ; Berg, G.C.M. van den; Joosten, M.H.A.J. ; Thomma, B.P.H.J. - \ 2014
PLoS One 9 (2014)2. - ISSN 1932-6203 - 14 p.
leucine-rich repeat - disease resistance protein - cladosporium-fulvum - arabidopsis-thaliana - endoplasmic-reticulum - hypersensitive response - verticillium resistance - plasma-membrane - innate immunity - kinase bri1
Resistance in tomato against race 1 strains of the fungal vascular wilt pathogens Verticillium dahliae and V. albo-atrum is mediated by the Ve locus. This locus comprises two closely linked inversely oriented genes, Ve1 and Ve2, which encode cell surface receptors of the extracellular leucine-rich repeat receptor-like protein (eLRR-RLP) type. While Ve1 mediates Verticillium resistance through monitoring the presence of the recently identified V. dahliae Ave1 effector, no functionality for Ve2 has been demonstrated in tomato. Ve1 and Ve2 contain 37 eLRRs and share 84% amino acid identity, facilitating investigation of Ve protein functionality through domain swapping. In this study it is shown that Ve chimeras in which the first thirty eLRRs of Ve1 were replaced by those of Ve2 remain able to induce HR and activate Verticillium resistance, and that deletion of these thirty eLRRs from Ve1 resulted in loss of functionality. Also the region between eLRR30 and eLRR35 is required for Ve1-mediated resistance, and cannot be replaced by the region between eLRR30 and eLRR35 of Ve2. We furthermore show that the cytoplasmic tail of Ve1 is required for functionality, as truncation of this tail results in loss of functionality. Moreover, the C-terminus of Ve2 fails to activate immune signaling as chimeras containing the C-terminus of Ve2 do not provide Verticillium resistance. Furthermore, Ve1 was found to interact through its C-terminus with the eLRR-containing receptor-like kinase (eLRR-RLK) interactor SOBIR1 that was recently identified as an interactor of eLRR-RLP (immune) receptors. Intriguingly, also Ve2 was found to interact with SOBIR1.
Development of ileal cytokine and immunoglobulin expression levels in response to early feeding in broilers and layers
Simon, K. ; Vries Reilingh, G. de; Kemp, B. ; Lammers, A. - \ 2014
Poultry Science 93 (2014)12. - ISSN 0032-5791 - p. 3017 - 3027.
immune-responses - gut microbiota - intestinal microbiota - natural antibodies - innate immunity - delayed access - axenic mice - performance - chickens - system
Provision of feed in the immediate posthatch period may influence interaction between intestinal microbiota and immune system, and consequently immunological development of the chick. This study addressed ileal immune development in response to early feeding in 2 chicken breeds selected for different production traits: broilers and layers. Chicks of both breeds either received feed and water immediately posthatch or were subjected to a 72-h feed and water delay. Ileal cytokine and immunoglobulin mRNA expression levels were determined at different time points. Effects of early feeding were limited, but breeds differed strikingly regarding cytokine and immunoglobulin expression levels. Cytokine expression levels in broilers were low compared with layers and showed a transient drop in the second to third week of life. In contrast, broilers showed considerably higher expression levels of IgA, IgM, and IgY. These findings indicate that the 2 breeds use different immune strategies, at least on the ileal level.
Evaluation of immune and apoptosis related gene responses using an RNAi approach in vaccinated Penaeus monodon during oral WSSV infection
Kulkarni, A.D. ; Caipang, C.M.A. ; Kiron, V. ; Rombout, J.H.W.M. ; Fernandes, J.M.O. ; Brinchmann, M. - \ 2014
Marine Genomics 18 (2014)part A. - ISSN 1874-7787 - p. 55 - 65.
spot-syndrome-virus - double-stranded-rna - black tiger shrimp - toll-like receptors - litopenaeus-vannamei - molecular-cloning - innate immunity - fenneropenaeus-chinensis - expression analysis - vibrio-anguillarum
In the present study RNA interference was used to elucidate the connection between two endogenous genes [Penaeus monodon Rab7 (PmRab7) or P. monodon inhibitor of apoptosis (PmIAP)], and selected immune/apoptosis-related genes in orally ‘vaccinated’ shrimp after white spot syndrome virus (WSSV) infection. P. monodon were vaccinated by feeding them with formalin inactivated WSSV-coated feed. Thereafter, PmRab7 or PmIAP genes were silenced by injecting the shrimps with their respective dsRNA. The resulting groups of shrimps, Rab7 and IAP, were orally infected with WSSV and the expression of three immune-relevant genes in Rab7 group and five apoptosis-related genes in IAP group was evaluated. In the Rab7 group, PmToll, PmPPAE 2 and Pm penaeidin genes were down-regulated. The IAP-silenced shrimps were characterized by down-regulation of Pm caspase, PmERp57, Pm14-3-3 e, Pm ald, and up-regulation of PmSTAT. Thus, silencing of PmRab7/PmIAP has provided important clues on their relationship with selected immune/apoptosis genes in orally vaccinated P. monodon during WSSV infection.
Early-life environmental variation affects intestinal microbiota and immune development in new-born piglets
Schokker, D.J. ; Zhang, J. ; Zhang, L.L. ; Vastenhouw, S.A. ; Heilig, H.G.H.J. ; Smidt, H. ; Rebel, J.M.J. ; Smits, M.A. - \ 2014
PLoS One 9 (2014)6. - ISSN 1932-6203
phylogenetic microarray analysis - large gene lists - gut microbiota - staphylococcus-aureus - innate immunity - responses - homeostasis - diversity - cytoscape - system
Background - Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timin Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timing and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings - To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance - We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. g and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. Figures
The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach
Viegas Calcada, D.I. ; Vianello, D. ; Giampieri, E. ; Sala, C. ; Castellani, G. ; Graaf, A. de; Kremer, B. ; Ommen, B. van; Feskens, E.J.M. ; Santoro, A. ; Franceschi, C. ; Bouwman, J. - \ 2014
Mechanisms of Ageing and Development 136-137 (2014). - ISSN 0047-6374 - p. 138 - 147.
nf-kappa-b - microarray experiment miame - minimum information - innate immunity - quantitative-analysis - interaction networks - insulin-resistance - cell biology - data sets - t-cells
Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems
The leucine-rich repeat receptor kinase BIR2 is a negative regulator of BAK1 in plant immunity
Halter, T. ; Imkampe, J. ; Mazzotta, S. ; Wierzba, M. ; Postel, S. ; Bücherl, C.A. ; Kiefer, C. ; Stahl, M. ; Chinchilla, D. ; Wang, X. ; Nürnberger, T. ; Zipfel, C. ; Clouse, S. ; Borst, J.W. ; Boeren, S. ; Vries, S.C. de; Tax, F. ; Kemmerling, B. - \ 2014
Current Biology 24 (2014)2. - ISSN 0960-9822 - p. 134 - 143.
innate immunity - cell-death - necrotrophic pathogens - molecular-patterns - protein-kinase - arabidopsis - complex - bri1 - perception - activation
Background Transmembrane leucine-rich repeat (LRR) receptors are commonly used innate immune receptors in plants and animals but can also sense endogenous signals to regulate development. BAK1 is a plant LRR-receptor-like kinase (RLK) that interacts with several ligand-binding LRR-RLKs to positively regulate their functions. BAK1 is involved in brassinosteroid-dependent growth and development, innate immunity, and cell-death control by interacting with the brassinosteroid receptor BRI1, immune receptors, such as FLS2 and EFR, and the small receptor kinase BIR1, respectively. Results Identification of in vivo BAK1 complex partners by LC/ESI-MS/MS uncovered two novel BAK1-interacting RLKs, BIR2 and BIR3. Phosphorylation studies revealed that BIR2 is unidirectionally phosphorylated by BAK1 and that the interaction between BAK1 and BIR2 is kinase-activity dependent. Functional analyses of bir2 mutants show differential impact on BAK1-regulated processes, such as hyperresponsiveness to pathogen-associated molecular patterns (PAMP), enhanced cell death, and resistance to bacterial pathogens, but have no effect on brassinosteroid-regulated growth. BIR2 interacts constitutively with BAK1, thereby preventing interaction with the ligand-binding LRR-RLK FLS2. PAMP perception leads to BIR2 release from the BAK1 complex and enables the recruitment of BAK1 into the FLS2 complex. Conclusions Our results provide evidence for a new regulatory mechanism for innate immune receptors with BIR2 acting as a negative regulator of PAMP-triggered immunity by limiting BAK1-receptor complex formation in the absence of ligands.
B-glucan-supplemented diets increase poly(I:C)-induced gene expression of Mx, possibly via Tlr3-mediated recognition mechanism in common carp (Cyprinus carpio)
Falco Gracia, J.A. ; Miest, J.J. ; Pionnier, N. ; Pietretti, D. ; Forlenza, M. ; Wiegertjes, G.F. ; Hoole, D. - \ 2014
Fish and Shellfish Immunology 36 (2014)2. - ISSN 1050-4648 - p. 494 - 502.
toll-like receptor-3 - aeromonas-salmonicida infection - zebrafish danio-rerio - cyprinus-carpio - clarias-batrachus - immune parameters - innate immunity - asian catfish - stranded-rna - l.
We have previously observed that in common carp (Cyprinus carpio), administration of ß-glucan (MacroGard®) as feed additive leads to a lower expression of pro-inflammatory cytokines suggesting that this immunostimulant may be preventing an acute and potentially dangerous response to infection, particularly in the gut. However, in general, mechanisms to detect and eliminate pathogens must also be induced in order to achieve an efficient clearance of the infection. Protection against viral diseases acquired through ß-glucan-supplemented feed has been extensively reported for several experimental models in fish but the underlining mechanisms are still unknown. Thus, in order to better characterize the antiviral action induced by ß-glucans in fish, MacroGard® was administered daily to common carp in the form of supplemented commercial food pellets. Carp were fed for a period of 25 days prior to intra-peritoneal injection with polyinosinic:polycytidylic acid (poly(I:C)), a well-known double-stranded RNA mimic that triggers a type-I interferon (IFN) response. Subsequently, a set of immune related genes, including mx, were analysed by real-time PCR on liver, spleen, head kidney and mid gut tissues. Results obtained confirmed that treatment with ß-glucan alone generally down-regulated the mRNA expression of selected cytokines when compared to untreated fish, while mx gene expression remained stable or was slightly up-regulated. Injection with poly(I:C) induced a similar down-regulated gene expression pattern for cytokines in samples from ß-glucan fed fish. In contrast, poly(I:C) injection markedly increased mx gene expression in samples from ß-glucan fed fish but hardly in samples from fish fed control feed. In an attempt to explain the high induction of mx, we studied Toll-like receptor 3 (TLR3) gene expression in these carp. TLR3 is a prototypical pattern recognition receptor considered important for the binding of viral double-stranded RNA and triggering of a type-I IFN response. Through genome data mining, two sequences for carp tlr3 were retrieved (tlr3.1 and tlr3.2) and characterized. Constitutive gene expression of both tlr3.1 and tlr3.2 was detected by real-time PCR in cDNA of all analysed carp organs. Strikingly, 25 days after ß-glucan feeding, very high levels of tlr3.1 gene expression were observed in all analysed organs, with the exception of the liver. Our data suggest that ß-glucan-mediated protection against viral diseases could be due to an increased Tlr3-mediated recognition of ligands, resulting in an increased antiviral activity of Mx.
Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.
Kaput, J. ; Ommen, B. van; Kremer, B. ; Priami, C. ; Pontes Monteiro, J. ; Morine, M. ; Pepping, F. ; Diaz, Z. ; Fenech, M. ; He, Y. ; Albers, R. ; Drevon, C.A. ; Evelo, C.T. ; Hancock, R.E.W. ; Ijsselmuiden, C. ; Lumey, L.H. ; Minihane, A.M. ; Muller, M.R. ; Murgia, C. ; Radonjic, M. ; Sobral, B.W.S. ; West Jr., K.P. - \ 2014
Genes & Nutrition 9 (2014)9. - ISSN 1555-8932 - 9 p.
birth-weight infants - developing-countries - global health - environmental enteropathy - participatory research - grand challenges - innate immunity - trace-elements - biology - nutrition
Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems’ responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.
Fungal endopolygalacturonases are recognized as MAMPs by the Arabidopsis Receptor-Like Protein RBPG1
Zhang, L. ; Kars, I. ; Essenstam, B. ; Liebrand, T.W.H. ; Wagemakers, L. ; Elberse, J. ; Tagkalaki, P. ; Tjoitang, D. ; Ackerveken, G. van den; Kan, J.A.L. van - \ 2014
Plant Physiology 164 (2014)1. - ISSN 0032-0889 - p. 352 - 364.
ethylene-inducing xylanase - agrobacterium-mediated transformation - innate immunity - nicotiana-benthamiana - necrotizing activity - enzymatic-activity - aspergillus-niger - plasma-membrane - plant immunity - active-site
Plants perceive microbial invaders using pattern recognition receptors that recognize microbe-associated molecular patterns. In this study, we identified RESPONSIVENESS TO BOTRYTIS POLYGALACTURONASES1 (RBPG1), an Arabidopsis (Arabidopsis thaliana) leucine-rich repeat receptor-like protein, AtRLP42, that recognizes fungal endopolygalacturonases (PGs) and acts as a novel microbe-associated molecular pattern receptor. RBPG1 recognizes several PGs from the plant pathogen Botrytis cinerea as well as one from the saprotroph Aspergillus niger. Infiltration of B. cinerea PGs into Arabidopsis accession Columbia induced a necrotic response, whereas accession Brno (Br-0) showed no symptoms. A map-based cloning strategy, combined with comparative and functional genomics, led to the identification of the Columbia RBPG1 gene and showed that this gene is essential for the responsiveness of Arabidopsis to the PGs. Transformation of RBPG1 into accession Br-0 resulted in a gain of PG responsiveness. Transgenic Br-0 plants expressing RBPG1 were equally susceptible as the recipient Br-0 to the necrotroph B. cinerea and to the biotroph Hyaloperonospora arabidopsidis. Pretreating leaves of the transgenic plants with a PG resulted in increased resistance to H. arabidopsidis. Coimmunoprecipitation experiments demonstrated that RBPG1 and PG form a complex in Nicotiana benthamiana, which also involves the Arabidopsis leucine-rich repeat receptor-like protein SOBIR1 (for SUPPRESSOR OF BIR1). sobir1 mutant plants did not induce necrosis in response to PGs and were compromised in PG-induced resistance to H. arabidopsidis.
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