Genetic and Non-Genetic Inheritance of Natural Antibodies Binding Keyhole Limpet Hemocyanin in a Purebred Layer Chicken Line
Berghof, T.V.L. ; Klein, S.A.S. van der; Arts, J.A.J. ; Parmentier, H.K. ; Poel, J.J. van der; Bovenhuis, H. - \ 2015
PLoS ONE 10 (2015)6. - ISSN 1932-6203 - 13 p.
laying hens - immune-responses - parameters - iga - survival - isotypes - associations - sensitivity - disease - cells
Natural antibodies (NAb) are defined as antibodies present in individuals without known antigenic challenge. Levels of NAb binding keyhole limpet hemocyanin (KLH) in chickens were earlier shown to be heritable, and to be associated with survival. Selective breeding may thus provide a strategy to improve natural disease resistance. We phenotyped 3,689 white purebred laying chickens for KLH binding NAb of different isotypes around 16 weeks of age. Heritabilities of 0.12 for the titers of total antibodies (IgT), 0.14 for IgM, 0.10 for IgA, and 0.07 for IgG were estimated. We also estimated high, positive genetic, and moderate to high, positive phenotypic correlations of IgT, IgM, IgA, and IgG, suggesting that selective breeding for NAb can be done on all antibody isotypes simultaneously. In addition, a relatively substantial non-genetic maternal environmental effect of 0.06 was detected for IgM, which may reflect a transgenerational effect. This suggests that not only the genes of the mother, but also the maternal environment affects the immune system of the offspring. Breaking strength and early eggshell whiteness of the mother’s eggs were predictive for IgM levels in the offspring, and partly explained the observed maternal environmental effects. The present results confirm that NAb are heritable, however maternal effects should be taken into account.
Enveloped virus-like particles as vaccines against pathogenic arboviruses
Pijlman, G.P. - \ 2015
Biotechnology Journal 10 (2015)5. - ISSN 1860-6768 - p. 659 - 670.
japanese encephalitis-virus - valley fever virus - west nile virus - dengue virus - insect cells - structural proteins - subviral particles - flavivirus vaccines - immune-responses - subunit vaccine
Arthropod-borne arboviruses form a continuous threat to human and animal health, but few arboviral vaccines are currently available. Advances in expression technology for complex, enveloped virus-like particles (eVLPs) create new opportunities to develop potent vaccines against pathogenic arboviruses. In this short review, I highlight the successes and challenges in eVLP production for members of the three major arbovirus families: Flaviviridae (e.g., dengue, West Nile, Japanese encephalitis); Bunyaviridae (e.g., Rift Valley fever); and Togaviridae (e.g., chikungunya). The results from pre-clinical testing will be discussed as well as specific constraints to the large-scale manufacture and purification of eVLPs, which are complex assemblies of membranes and viral glycoproteins. Insect cells emerge as ideal substrates for correct arboviral glycoprotein folding and posttranslational modification to yield high quality eVLPs. Furthermore, baculovirus expression in insect cell culture is scalable and has a proven safety record in industrial human and veterinary vaccine manufacturing. In conclusion, eVLPs produced in insect cells using modern biotechnology have a realistic potential to be used in novel vaccines against arboviral diseases.
Association of natural (auto-) antibodies in young gilts with osteochondrosis at slaughter
Koning, D.B. de; Damen, E.P.C.W. ; Nieuwland, M.G.B. ; Grevenhof, E.M. van; Hazeleger, W. ; Kemp, B. ; Parmentier, H.K. - \ 2015
Livestock Science 176 (2015). - ISSN 1871-1413 - p. 152 - 160.
serum-free culture - growth cartilage - epiphyseal growth - immune-responses - growing gilts - dairy-cows - chondrocytes - pigs - proteoglycans - lesions
Osteochondrosis (OC) develops at a young age and has been associated with lameness and reduced longevity of sows. Early detection of OC is therefore beneficial for selection against OC. Possibly, immunological components within the blood may serve as an indicator for OC development and could therefore be used as a biomarker. Levels of naturally occurring (auto-) antibodies (N[A]Ab) have been associated with homeostatic imbalance and various forms of inflammation, and may have an association with OC. The aim of this study was to investigate possible associations between the presence and levels of N(A)Ab of the IgM and IgG isotypes at an early age with OC in growing gilts at slaughter (24 weeks of age). Plasma samples were obtained from 212 Topigs 20 (Dutch Large White x Dutch Landrace) gilts at 6, 10, and 24 weeks of age and analyzed for N(A)Ab titers against 11 (auto-) antigens using ELISA. After slaughter, the elbow, hock, and knee joints were macroscopically examined for OC status. Due to low prevalence of OC in the elbow joint (5.4%), the elbow joint was not taken into account in analyses. Significant (P=0.05) associations with OC in both the hock joint and at the animal level (all joints combined) were found for IgM titers against chondroitin sulfate A at 6 weeks of age (OR 1.4 and 1.5), actin at 6 weeks of age (OR 1.4 and 1.3), thyroglobulin at 24 weeks of age (OR 1.5 and 1.3), and IgG titers against insulin at 6 weeks of age (OR 1.7 and 1.4). Additionally, significant (P=0.05) associations with OC were found at the knee joint for IgM titers against albumin at 6 weeks of age (OR 2.3), at the hock joint for IgM titers against keyhole limpet hemocyanin at 6 weeks of age (OR 1.4), and at the animal level for IgM titers against actin at 24 weeks of age (OR 1.3). This study indicated for the first time associations between the presence and levels of N(A)Ab at a young age and OC at 24 weeks of age in breeding gilts.
Phenotypic and genetic relationships of bovine natural antibodies binding keyhole limpet hemocyanin in plasma and milk
Klerk, B. de; Ducro, B.J. ; Heuven, H.C.M. ; Uyl, I. den; Arendonk, J.A.M. van; Parmentier, H.K. ; Poel, J.J. van der - \ 2015
Journal of Dairy Science 98 (2015)4. - ISSN 0022-0302 - p. 2746 - 2752.
immune-responses - autoantibodies - cows - parameters - survival - titers
To improve the health status (resilience) of dairy cows, levels of natural antibodies (NAb) might be useful. The objective of the present study was to compare levels and to estimate genetic parameters for NAb measured in milk and plasma samples. Titers of NAb IgM and IgG isotype-binding keyhole limpet hemocyanin of 2,919 cows, in both plasma and milk, were measured using ELISA. Analysis revealed that NAb levels in milk significantly increased with parity, whereas they remained constant in plasma. Moderate positive phenotypic correlations were found between NAb levels in milk and in plasma: 0.18 for IgG and 0.40 for IgM. This indicates that NAb from milk and plasma might reflect different aspects of dairy cow health status. However, high genetic correlations were found for NAb in milk and plasma: 0.81 for IgG and 0.79 for IgM. Heritabilities (SE in parentheses) for NAb measured in plasma [0.15 (0.05) for IgG and 0.25 (0.06) for IgM] were higher than heritabilities of NAb measured in milk [0.08 (0.03) for IgG and 0.23 (0.05) for IgM]. Our results indicate that NAb measured in milk and plasma are heritable and likely have a common genetic background, suggesting that NAb levels measured in milk might be useful for genetic improvement of disease resistance.
No significant differences in the breadth of the foot-and-mouth disease serotype A vaccine induced antibody responses in cattle, using different antigens, mixed antigens and different toutes of administration
Tekleghiorghis, T. ; Weerdmeester, K. ; Hemert-Kluitenberg, F. ; Moormann, R.J.M. ; Dekker, A. - \ 2014
Vaccine 32 (2014)41. - ISSN 0264-410X - p. 5330 - 5336.
aluminum hydroxide gel - emergency vaccination - immune-responses - cross-protection - fmd vaccines - virus - elisa - potency - tests - challenge
Inactivated whole virus foot-and-mouth disease (FMD) vaccines are used worldwide for protection against FMD, but not all vaccines induce protection against all genetic variants of the same FMD virus serotype. The aim of this study is to investigate whether the “breadth” of the antibody response against different strains of the same FMD virus serotype in cattle could be improved by using a different adjuvant, a mix of antigens and/or different routes of administration. To this end, six groups of five cattle were vaccinated with different FMD virus serotype A strain vaccines formulated with Montanide ISA 206 VG adjuvant. Antibody responses for homologous and heterologous cross-reactivity against a panel of 10 different FMD virus serotype A strains were tested by a liquid-phase blocking ELISA. Results of cattle vaccinated with ISA 206 VG adjuvanted vaccine were compared with results obtained in a previous study using aluminium hydroxide-saponin adjuvant. No significant effect of adjuvant on the breadth of the antibody response was observed, neither for mixing of antigens nor for the route of administration (subcutaneous vs. intradermal). Comparison of antigen payload, however, increased both homologous and heterologous titres; a 10-fold higher antigen dose resulted in approximately four times higher titres against all tested strains. Our study shows that breadth of the antibody response depends mainly on the vaccine strain; we therefore propose that, for vaccine preparation, only FMD virus strains are selected that, among other important characteristics, will induce a wide antibody response to different field strains.
Lung pathogenicity of European genotype 3 strain porcine reproductive and respiratory syndrome virus (PRRSV) differs from that of subtype 1 strains.
Weesendorp, E. ; Rebel, J.M.J. ; Popma-de Graaf, D.J. ; Fijten, H.P.D. ; Stockhofe, N. - \ 2014
Veterinary Microbiology 174 (2014)1-2. - ISSN 0378-1135 - p. 127 - 138.
experimentally infected-pigs - lelystad virus - immunological responses - immune-responses - swine - cells - disease - expression - cytokines - virulence
Porcine reproductive and respiratory syndrome (PRRS) is difficult to control due to a high mutation rate of the PRRS virus (PRRSV) and the emergence of virulent strains. The objective of this study was to analyse early and late pathological responses in the respiratory tract after infection with the European PRRSV subtype 3 strain Lena in comparison to two European PRRSV subtype 1 strains: Belgium A and Lelystad-Ter Huurne (LV). For each virus strain, groups of twelve pigs were inoculated, and four pigs per group were euthanized at days 3, 7 and 35 post-infection (p.i.) for consecutive examination. Infection with strain Lena resulted in a more severe disease than with the subtype 1 strains, an inflammatory response within the first week of infection with expression of IL-1a in the lung and lymph node, and an influx of neutrophils and monocytes in bronchoalveolar lavage fluid (BALF). Infection with strain Belgium A or LV resulted in mild or no pathology within the first week of infection, but inflammatory cell influx in the lung interstititium was increased at the end of the experiment at day 35 p.i. At five weeks p.i., all strains induced a higher percentage of cytotoxic T cells and higher levels of IFN-¿ producing cells in BALF. This might have contributed to clearance of virus. In general, subtype 3 strain Lena induced a stronger early inflammatory response which led to more severe clinical disease and pathology. On the other hand, this may have supported an enhanced or faster clearance of virus in tissues, compared to subtype 1 strains.
Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus.
Peeters, B.P.H. ; Tonnis, W.F. ; Murugappan, S. ; Rottier, P. ; Koch, G. ; Frijlink, H.W. ; Huckriede, A. ; Hinrichs, W.L.J. - \ 2014
Vaccine 32 (2014)48. - ISSN 0264-410X - p. 6445 - 6450.
a h5n1 - aerosol vaccination - immune-responses - mass vaccination - powder - transmission - delivery - poultry - inulin - birds
Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is, however, problematic in emergency situations, e.g. during outbreaks in poultry, as there are currently no mass application methods to effectively vaccinate large numbers of birds within a short period of time. To evaluate the suitability of needle-free pulmonary immunization for mass vaccination of poultry against HPAI H5N1, we performed a proof-of-concept study in which we investigated whether non-adjuvanted spray-freeze-dried (SFD) whole inactivated virus (WIV) can be used as a dry powder aerosol vaccine to immunize chickens. Our results show that chickens that received SFD-WIV vaccine as aerosolized powder directly at the syrinx (the site of the tracheal bifurcation), mounted a protective antibody response after two vaccinations and survived a lethal challenge with HPAI H5N1. Furthermore, both the number of animals that shed challenge virus, as well as the level of virus shedding, were significantly reduced. Based on antibody levels and reduction of virus shedding, pulmonary vaccination with non-adjuvanted vaccine was at least as efficient as intratracheal vaccination using live virus. Animals that received aerosolized SFD-WIV vaccine by temporary passive inhalation showed partial protection (22% survival) and a delay in time-to-death, thereby demonstrating the feasibility of the method, but indicating that the efficiency of vaccination by passive inhalation needs further improvement. Altogether our results provide a proof-of-concept that pulmonary vaccination using an SFD-WIV powder vaccine is able to protect chickens from lethal HPAI challenge. If the efficacy of pulmonary vaccination by passive inhalation can be improved, this method might be suitable for mass application.
Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge
Doel, P. van den; Volz, A. ; Roose, J.M. ; Sewbalaksing, V.D. ; Pijlman, G.P. ; Middelkoop, I. van; Duiverman, V. ; Wetering, E. van de; Sutter, G. ; Osterhaus, A.D. ; Martina, B.E. - \ 2014
PLoS Neglected Tropical Diseases 8 (2014)9. - ISSN 1935-2727 - 12 p.
indian-ocean islands - reunion island - neutralizing antibodies - nonhuman-primates - immune-responses - adult patients - insect cells - dna vaccine - infection - mva
Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.
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.
Prevalence and potential influencing factors of non-nutritive oral behaviors of veal calves on commercial farms
Leruste, H. ; Brscic, M. ; Cozzi, G. ; Kemp, B. ; Wolthuis-Fillerup, M. ; Lensink, B.J. ; Bokkers, E.A.M. ; Reenen, C.G. van - \ 2014
Journal of Dairy Science 97 (2014)11. - ISSN 0022-0302 - p. 7021 - 7030.
immune-responses - housing systems - dairy calves - risk-factors - welfare - sucking - intersucking - stereotypies - reliability - indicators
Veal calves raised under intensive conditions may express non-nutritive oral behaviors. When expressed in an abnormal way, these behaviors can be a sign of mental suffering and reduced welfare due to a mismatch between environmental or management features and animals' needs. The aims of this study were to estimate the prevalence of non-nutritive oral behaviors in a large sample of veal farms in Europe and to determine the potential influencing factors present at farm level. Data were collected on 157 commercial veal farms in the 3 main veal-producing countries in Europe (the Netherlands, France, and Italy). Observations of 3 non-nutritive oral behaviors (manipulating substrates, tongue rolling, and manipulating a penmate) were performed when calves were aged 14 wk, and the prevalence of these behaviors was calculated. Information on management practices and characteristics of the building and equipment were collected on all farms to assess potential influencing factors for each of the 3 behaviors. Odds ratios and 95% confidence intervals were calculated to evaluate the effect of each individual factor within a generalized linear model. The mean percentage of calves per farm performing manipulating substrates was 11.0 ± 0.46%, performing tongue rolling 2.8 ± 0.18%, and manipulating a penmate 2.7 ± 0.09%, with a high range between farms. Allowing more space for calves than the legal minimum requirement of 1.8 m2/calf and housing them in groups of >10 calves/pen reduced the incidences of manipulating substrates and tongue rolling. Incidence of manipulating substrates was lower for calves fed maize silage compared with calves fed cereal grain, pellets, or muesli. A higher risk of tongue rolling was found when baby-boxes (i.e., single housing during the first 5 to 8 wk) were not used. Risk of calves manipulating a penmate was higher for calves of milk- or meat-type breeds compared with dual-purpose breeds and for calves fed with 280 to 380 kg compared with those fed >380 kg of milk powder in total for the fattening period. The study allowed assessment of multiple factors across farms that showed variety in terms of conditions and level of non-nutritive oral behaviors. Identification of the factors influencing non-nutritive oral behavior is helpful to define potential actions that could be taken on farms to improve the welfare of calves and reduce the prevalence of these behaviors.
One health approach to Rift Valley fever vaccine development
Kortekaas, J.A. - \ 2014
Antiviral Research 106 (2014)24. - ISSN 0166-3542 - p. 24 - 32.
lethal virus challenge - saudi-arabia - immune-responses - rhesus macaques - mp-12 vaccine - south-africa - enzootic hepatitis - northeastern kenya - ifnar(-/-) mice - rvfv infection
Since its discovery in the 1930s, Rift Valley fever virus (RVFV) spread across the African continent and invaded the Arabian Peninsula and several islands off the coast of Southeast Africa. The virus causes recurrent outbreaks in these regions, and its continued spread is of global concern. Next-generation veterinary vaccines of improved efficacy and safety are being developed that can soon be used for the widespread vaccination of livestock. However, due to regulatory and economic challenges, vaccine manufacturers have been reluctant to develop a human vaccine. Recent innovations in veterinary vaccinology, animal models and licensing strategies can now be used to overcome these hurdles. This paper reviews the historical impact of RVFV on human health and proposes strategies to develop and license a next-generation vaccine for both animals and humans
Identification of factors associated with increased excretion of foot-and-mouth disease virus
Bravo De Rueda, C. ; Dekker, A. ; Eble, P.L. ; Jong, M.C.M. de - \ 2014
Preventive Veterinary Medicine 113 (2014)1. - ISSN 0167-5877 - p. 23 - 33.
immune-responses - dairy-cows - transmission - vaccination - pigs - infection - quantification - epidemiology - calves - lambs
We investigated which variables possibly influence the amount of foot-and-mouth disease virus (FMDV) shed in secretions and excretions by FMDV infected animals, as it is likely that the amount of FMDV shed is related to transmission risk. First, in a separate analysis of laboratory data, we showed that the total amount of FMDV in secretions and excretions from infected animals is highly correlated with maximum titres of FMDV. Next, we collected data from 32 published scientific articles in which FMDV infection experiments were described. The maximum titres of FMDV reported in different secretions and excretions (the response variable) and the experimental conditions in which they occurred (the explanatory variables), were recorded in a database and analyzed using multivariate regression models with and without random effects. In both types of models, maximum titres of FMDV were significantly (p <0.05) associated with types of secretions and excretions, animal species, stage of the disease and days post infection. These results can be used to prioritize biosecurity measures in contingency plans.
Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion
Diepen, J.A. van; Stienstra, R. ; Vroegrijk, I.O.C.M. ; Berg, S.A.A. van den; Salvatori, D. ; Hooiveld, G.J.E.J. ; Kersten, A.H. ; Tack, C.J. ; Netea, M.G. ; Smit, J.W.A. ; Joosten, L.A.B. ; Havekes, L.M. ; Dijk, K.W. van; Rensen, P.C.N. - \ 2013
Journal of Lipid Research 54 (2013)2. - ISSN 0022-2275 - p. 448 - 456.
lipid-metabolism - adipose-tissue - fatty-acids - lipoprotein metabolism - insulin-resistance - immune-responses - inflammation - liver - inflammasomes - interleukin-1
Caspase-1 is known to activate the proinflammatory cytokines IL-1 beta and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [H-3] TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [H-3] TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins.(jlr) The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion.-van Diepen, J. A., R. Stienstra, I. O. C. M. Vroegrijk, S. A. A. van den Berg, D. Salvatori, G. J. Hooiveld, S. Kersten, C. J. Tack, M. G. Netea, J. W. A. Smit, L. A. B. Joosten, L. M. Havekes, K. W. van Dijk, and P. C. N. Rensen. Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion. J. Lipid Res. 2013. 54: 448-456.
IgG antibodies in food allergy influence allergen-antibody complex formation and binding to B cells: a role for complement receptors
Meulenbroek, L.A. ; Jong, R.J. ; Hartog Jager, C.F. den; Monsuur, H.N. ; Wouters, D. ; Nauta, A. ; Knippels, L.M. ; Neerven, R.J.J. van; Ruiter, B. ; Leusen, J.H. ; Hack, C.E. ; Bruijnzeel-Koomen, C.A. ; Knulst, A.C. ; Garssen, J. ; Hoffen, E. van - \ 2013
The Journal of Immunology 191 (2013)7. - ISSN 0022-1767 - p. 3526 - 3533.
immune-responses - antigen presentation - blocking antibodies - natural antibody - peanut allergy - double-blind - fc regions - t-cells - activation - inhibition
Allergen-IgE complexes are more efficiently internalized and presented by B cells than allergens alone. It has been suggested that IgG Abs induced by immunotherapy inhibit these processes. Food-allergic patients have high allergen-specific IgG levels. However, the role of these Abs in complex formation and binding to B cells is unknown. To investigate this, we incubated sera of peanut- or cow's milk-allergic patients with their major allergens to form complexes and added them to EBV-transformed or peripheral blood B cells (PBBCs). Samples of birch pollen-allergic patients were used as control. Complex binding to B cells in presence or absence of blocking Abs to CD23, CD32, complement receptor 1 (CR1, CD35), and/or CR2 (CD21) was determined by flow cytometry. Furthermore, intact and IgG-depleted sera were compared. These experiments showed that allergen-Ab complexes formed in birch pollen, as well as food allergy, contained IgE, IgG1, and IgG4 Abs and bound to B cells. Binding of these complexes to EBV-transformed B cells was completely mediated by CD23, whereas binding to PBBCs was dependent on both CD23 and CR2. This reflected differential receptor expression. Upon IgG depletion, allergen-Ab complexes bound to PBBCs exclusively via CD23. These data indicated that IgG Abs are involved in complex formation. The presence of IgG in allergen-IgE complexes results in binding to B cells via CR2 in addition to CD23. The binding to both CR2 and CD23 may affect Ag processing and presentation, and (may) thereby influence the allergic response.
In vivo screening of five phytochemicals/extracts and a fungal immunomodulatory protein against colibacillosis in broilers
Peek, H.W. ; Halkes, S.B.A. ; Mes, J.J. ; Landman, W.J.M. - \ 2013
Veterinary Quarterly 33 (2013)3. - ISSN 0165-2176 - p. 132 - 138.
dietary betaine - avian eimeria - herb polysaccharides - anticoccidial drugs - immune-responses - coccidiosis - tenella - chicks - resistance - performance
Besides the anticoccidial drug resistance problem, increasing consumer concerns about food safety and residues have propelled the quest for alternative prevention and control strategies amongst which phytotherapy has gained appeal due to a renewed interest in natural medicine.Objective: The objective was in vivo screening of four phytochemicals/extracts and a fungal immunomodulatory protein (FIP) against an Eimeria acervulina infection in broilers.Animals and methods: Four phytochemicals/extracts (extract from Echinacea purpurea, betaine (Betain™), curcumin, carvacrol (two different doses)), and a recombinant FIP from Ganoderma lucidum cloned and expressed in Escherichia coli were investigated for their anticoccidial potential. The experiment was conducted in a battery cage trial with 54 cages of eight birds each. Broilers infected with E. acervulina (a low and high infection dose of 104 and 105 sporulated oocysts, respectively) and treated with the phytochemicals/extracts or the FIP were compared with broilers treated with the anticoccidial salinomycin sodium (Sacox®) and with an untreated uninfected and an untreated infected control group. Coccidiosis lesion scores, body weight gains and oocyst shedding were used as parameters.Results: The results showed a coccidiosis infection dose effect on the mean coccidiosis lesion scores. The phytochemicals/extracts and the FIP failed to reduce coccidiosis lesion scores and oocyst shedding, while salinomycin efficiently controlled the E. acervulina infection and enabled significantly higher body weight gains.Conclusion: In conclusion, the selected phytochemicals/extracts and the FIP did not reduce the lesions of an experimentally induced E. acervulina infection.
In vivo screening of five phytochemicals/extracts and a fungal immunomodulatory protein against colibacillosis in broilers
Peek, H.W. ; Halkes, S.B.A. ; Tomassen, M.M.M. ; Mes, J.J. ; Landman, W.J.M. - \ 2013
Avian Pathology 42 (2013)3. - ISSN 0307-9457 - p. 235 - 247.
infectious-bronchitis virus - eimeria-tenella - immune-responses - dietary betaine - antimicrobial resistance - herb polysaccharides - commercial broilers - ganoderma-lucidium - escherichia-coli - chicks
Five phytochemicals/extracts (an extract from Echinacea purpurea, a ß-glucan-rich extract from Shiitake, betaine [Betain™], curcumin from Curcuma longa [turmeric] powder, carvacrol and also a recombinant fungal immunomodulatory protein [FIP] from Ganoderma lucidum) cloned and expressed in Escherichia coli were investigated for their anticolibacillosis potential in three chicken experiments, which were conducted in floor pens. Birds that were inoculated with E. coli intratracheally were treated with the phytochemicals/extracts or the FIP and compared with doxycycline-medicated and non-medicated infected broilers. Non-medicated and non-infected birds were used as negative controls. Mortality, colibacillosis lesions and body weight gains were used as parameters. Considering the sum of dead birds and chickens with generalized colibacillosis per group, there was no significant difference between the positive control groups and birds treated with phytochemicals/extracts or the FIP. In contrast, doxycycline-treated birds showed significantly lower mortality and generalized colibacillosis. Moreover, none of the phytochemicals/extracts and the FIP improved recovery from colibacillosis lesions, while all doxycycline-treated broilers recovered completely. The negative control birds and doxycycline-treated groups consistently showed the highest weight gains. Pulsed-field gel electrophoresis of reisolates showed that they were genetically indistinguishable from the inoculation strain. In conclusion, none of the tested phytochemicals/extracts and the FIP significantly reduced the E. coli-induced mortality and generalized colibacillosis, and nor did they improve recovery from colibacillosis lesions.
Phenotypic modulation and cytokine profiles of antigen presenting cells by European subtype 1 and 3 porcine reproductive and respiratory syndrome virus strains in vitro and in vivo
Weesendorp, E. ; Stockhofe-Zurwieden, N. ; Popma-de Graaf, D.J. ; Fijten, H.P.D. ; Rebel, J.M.J. - \ 2013
Veterinary Microbiology 167 (2013)3-4. - ISSN 0378-1135 - p. 638 - 650.
dendritic cells - immune-responses - pigs - prrsv - infection - apoptosis - genotype - disease - lungs - interleukin-10
Porcine reproductive and respiratory syndrome virus (PRRSV) causes continuous problems in the pig industry, due to high costs of outbreaks and reduced welfare of diseased pigs. The severity of infection is, partly, dependent on the virus strain. Recently isolated Eastern-European subtype 3 strains are more pathogenic than the widespread subtype 1 strains. There is, however, almost no information available about the mechanisms involved in the pathogenicity of these subtype 3 strains. The objective of the present study was to characterize the in vitro and in vivo response of two European subtype 1 strains, Belgium A and Lelystad-Ter Huurne (LV), and a virulent subtype 3 strain, Lena, in bone marrow-derived dendritic cells (BM-DC) (in vitro) and alveolar macrophages (in vitro and in vivo). It was shown that infection with the Lena strain resulted in a higher apoptosis of cells in vitro and a higher level of infectivity in vitro and in vivo than the other virus strains. Furthermore, infection with Lena resulted in a small downregulation of the immunologically relevant cell surface molecules SLA-I, SLA-II and CD80/86 in vitro, and SLA-II in vivo. In spite of these differences, in vitro cytokine responses did not differ significantly between strains, except for the absence of IL-10 production by Lena in BM-DC. The higher infectivity, apoptosis and downregulation of the cell surface molecules, may have contributed to the increased pathogenicity of Lena, and have dampened specific immune responses. This could explain the delayed and decreased adaptive immune responses observed after infections with this strain.
Diversity of human small intestinal Streptococcus and Veillonella populations
Bogert, B. van den; Erkus, O. ; Boekhorst, J. te; Goffau, M. ; Smid, E.J. ; Zoetendal, E.G. ; Kleerebezem, M. - \ 2013
FEMS microbiology ecology 85 (2013)2. - ISSN 0168-6496 - p. 376 - 388.
human gastrointestinal-tract - multiple sequence alignment - desorption ionization-time - flight mass-spectrometry - high-throughput - gut microbiome - molecular analysis - genetic diversity - immune-responses - oral-cavity
Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points
Immunoglobulins drive terminal maturation of splenic dendritic cells
Zietara, N. ; Lyszkiewicz, M. ; Puchalka, J. ; Gutierrez, M.G. ; Lienenklaus, S. ; Hobeika, E. ; Reth, M. ; Martins Dos Santos, V.A.P. ; Krueger, A. ; Weiss, S. - \ 2013
Proceedings of the National Academy of Sciences of the United States of America 110 (2013)6. - ISSN 0027-8424 - p. 2282 - 2287.
c-type lectin - cross-presentation - antigen presentation - in-vivo - functional maturation - complement receptors - immune-responses - b-lymphocytes - self-antigens - t-cells
Nature and physiological status of antigen-presenting cells, such as dendritic cells DCs, are decisive for the immune reactions elicited. Multiple factors and cell interactions have been described that affect maturation of DCs. Here, we show that DCs arising in the absence of immunoglobulins (Ig) in vivo are impaired in cross-presentation of soluble antigen. This deficiency was due to aberrant cellular targeting of antigen to lysosomes and its rapid degradation. Function of DCs could be restored by transfer of Ig irrespective of antigen specificity and isotype. Modulation of cross-presentation by Ig was inhibited by coapplication of mannan and, thus, likely to be mediated by C-type lectin receptors. This unexpected dependency of splenic DCs on Ig to cross-present antigen provides insights into the interplay between cellular and humoral immunity and the immunomodulatory capacity of Ig
Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice
Reikvam, D.H. ; Derrien, M.M.N. ; Islam, R. ; Erofeev, A. ; Grcic, V. ; Sandvik, A. ; Gaustad, P. ; Meza-Zepeda, L.A. ; Jahnsen, F.L. ; Smidt, H. ; Johansen, F.E. - \ 2012
European journal of immunology 42 (2012)11. - ISSN 0014-2980 - p. 2959 - 2970.
gut microbiota - immune-responses - intestinal microbiota - secretory antibodies - immunoglobulin receptor - maintain homeostasis - colitis - disease - inflammation - environment
Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of the first line of natural or adaptive antibody-mediated immune defense of the intestinal mucosa. We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and upregulated the expression of antimicrobial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium-induced colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened.