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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    Improving disease resistance in chickens: divergent selection on natural antibodies
    Berghof, T.V.L. ; Poel, J.J. van der; Arts, J.A.J. ; Bovenhuis, H. ; Visker, M.H.P.W. ; Parmentier, H.K. - \ 2019
    - p. 507 - 507.
    Natural antibodies (NAb) are antibodies recognizing antigens without previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)-binding NAb titers in chickens are heritable, and higher KLH-binding NAb titers have been associated with higher survival. This suggests that breeding for higher NAb titers might improve general disease resistance. A purebred White Leghorn chicken line was divergently selected and bred on total KLH-binding NAb titers at 16 weeks of age for 6 generations, and resulted in a High and Low line. The average estimated breeding value differences in KLH-binding NAb titers increased with 0.36 for total, 0.40 for IgM, and 0.32 for IgG per generation. Generations 4 and 6 of the selection lines were inoculated with an avian pathogenic Escherichia coli (APEC) at 8 days of age. Mortality and morbidity after 1 week were signicantly reduced in the High line compared to the Low line, which suggests a higher APEC resistance in the High line compared to the Low line. To investigate possible correlated responses on the immune system, several traits were measured at different ages in several generations: the High line showed higher different NAb titers at different ages, antibody concentrations, percentage of antibody-producing B cells, and bursa weight at young age compared to the Low line. This suggests that KLH-binding NAb selection has a favourable correlated response on the humoral adaptive immune system. No line differences were observed for T cells, γδ T cells, natural killer (NK) cells, and antigen-presenting cells (APC). This might indicate that the selection had no unfavourable correlated responses on other parts of the immune system. This selection experiment shows that selective breeding on total KLH-binding NAb titers at 16 weeks of age is possible, and that selection for higher NAb has a benecial effect on resistance to APEC infection. In addition, the selection experiment suggests a promising opportunity for improving general disease resistance without unfavourable correlated selection responses.
    Genome-wide association study identifies loci influencing natural antibody titers in milk of Dutch Holstein-Friesian cattle
    Cordero-Solorzano, Juan ; Parmentier, Henk K. ; Arts, Joop A.J. ; Poel, Jan van der; Koning, Dirk Jan de; Bovenhuis, Henk - \ 2019
    Journal of Dairy Science 102 (2019)12. - ISSN 0022-0302 - p. 11092 - 11103.
    dairy cattle - genome-wide association study - immunoglobulin - natural antibody

    Natural antibodies (NAb) are produced without any antigenic stimulation as a part of the innate immune system and provide a first line of defense against pathogens. Hence, they may be a useful trait when estimating an animal's potential immune competence and in selection for disease resistance. The aim of this study was to identify genomic regions associated with different NAb traits in milk and potentially describe candidate genes. Milk samples from 1,695 first-lactation Holstein Friesian cows with titer measurements for keyhole limpet hemocyanin, lipopolysaccharide, lipoteichoic acid, and peptidoglycan-binding total NAb and isotypes IgG1, IgM, and IgA were used. Genome-wide association study analyses were performed using imputed 777K SNP genotypes, accounting for relationships using pedigree information. Functional enrichment analysis was performed on the significantly associated genomic regions to look for candidate genes. For IgM NAb, significant associations (false discovery rate <0.05) were found on Bos taurus autosome (BTA) 17, 18, and 21 with candidate genes related to immunoglobulin structure and early B cell development. For IgG1, associations were found on BTA3, and we confirmed a quantitative trait loci on BTA21 previously reported for IgG NAb in serum. Our results provide new insights into the regulation of milk NAb that will help unravel the complex relationship between milk immunoglobulins and disease resistance in dairy cattle.

    Investigation of a (putative) causal mutation in Toll-like receptor family member 1A in chickens
    Berghof, T.V.L. ; Voogdt, Carlos G.P. ; Arts, J.A.J. ; Bovenhuis, H. ; Parmentier, H.K. ; Poel, J.J. van der; Putten, Jos P.M. Van; Visker, M.H.P.W. - \ 2019
    Selective breeding for high natural antibody level increases resistance to avian pathogenic Escherichia coli (APEC) in chickens
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Poel, J.J. van der; Visker, M.H.P.W. ; Parmentier, H.K. - \ 2019
    Developmental and Comparative Immunology 93 (2019). - ISSN 0145-305X - p. 45 - 57.
    APEC - Breeding - Chicken - Disease resistance - Escherichia coli - Natural antibody

    Keyhole limpet hemocyanin (KLH)-binding natural antibody (NAb) titers in chickens are heritable, and higher levels have previously been associated with a higher survival. This suggests that selective breeding for higher NAb levels might increase survival by means of improved general disease resistance. Chickens were divergently selected and bred for total NAb levels binding KLH at 16 weeks of age for six generations, resulting in a High NAb selection line and a Low NAb selection line. To for test differences in disease resistance, chickens were challenged with avian pathogenic Escherichia coli (APEC) in two separate experiments. Chickens at 8 days of age received one of four intratracheal inoculations of 0.2 mL phosphate buffered saline (PBS): 1) mock inoculate, 2) with 0.2 mL PBS containing 108.20 colony-forming units (CFU)/mL APEC, 3) with 0.2 mL PBS containing 106.64 CFU/mL APEC, and 4) with 0.2 mL PBS containing 107.55 CFU/mL APEC. Mortality was recorded during 7 days post inoculation. Overall, 50–60% reduced mortality was observed in the High line compared to the Low line for all APEC doses. In addition, morbidity was determined of the surviving chickens at 15 days of age. The High line had lower morbidity scores compared to the Low line. We conclude that selective breeding for high KLH-binding NAb levels at 16 weeks of age increase APEC resistance in early life. This study and previous studies support the hypothesis that KLH-binding NAb might be used as an indicator trait for to selective breed for general disease resistance in an antigen non-specific fashion.

    A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows
    Klerk, Britt de; Emam, Mehdi ; Thompson-Crispi, Kathleen A. ; Sargolzaei, Mehdi ; Poel, Jan van der; Mallard, Bonnie A. - \ 2018
    Wageningen University and Research
    Genome-Wide Association Study - Natural antibody - Dairy cattle - Immune system - Veicle trafficking - Immunoglobulin class switching
    Background: Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. NAb are poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be a key trait when evaluating an animal’s potential natural disease resistance. Variation in NAb is caused by both genetic and environmental factors. In this study genetic parameters of NAb were estimated and a genome-wide association study (GWAS) was performed to gain further understanding on the genes that are responsible for the observed genetic variation of NAb in Canadian Holsteins. Results In total, blood samples of 1327 cows from 64 farms were studied. NAb binding to keyhole limpet hemocyanin (KLH) were determined via indirect ELISA. Immunoglobulin (Ig) isotypes, IgG and IgM, were evaluated. From the sample population, 925 cows were genotyped for 45,187 markers and each individual marker was tested to detect genetic variation in NAb levels. The relationships among animals was accounted for with genomic relationship. Results show heritabilities of 0.27 ± 0.064 (IgG) and 0.31 ± 0.065 (IgM). In total, 23 SNPs were found to be associated with IgG, but no SNPs were associated with IgM (FDR p-value < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.
    Selective breeding on natural antibodies in chickens: selection response, and correlated responses
    Berghof, T.V.L. ; Poel, J.J. van der; Arts, J.A.J. ; Bovenhuis, H. ; Visker, M.H.P.W. ; Parmentier, H.K. - \ 2018
    Breeding for high natural antibody levels reduces impact of E. coli (APEC) challenge in chickens
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Poel, J.J. van der; Parmentier, H.K. ; Visker, M.H.P.W. ; Parmentier, H.K. - \ 2018
    Body weight variation as indicator for resilience in chickens
    Berghof, T.V.L. ; Bovenhuis, H. ; Arts, J.A.J. ; Karangali, Francois ; Poel, J.J. van der; Parmentier, H.K. ; Mulder, H.A. - \ 2018

    Candidate gene for natural immune competence in chickens revealed through genome wide association study
    Visker, M.H.P.W. ; Berghof, T.V.L. ; Arts, J.A.J. ; Parmentier, H.K. ; Poel, J.J. van der; Vereijken, Addie ; Bovenhuis, H. - \ 2018
    In: Proceedings of the World Congress on Genetics Applied to Livestock Production. - WCGALP - 4 p.
    Natural antibodies (NAb) are antibodies that are present in individuals without prior exposure to the antigen that they bind. In chickens, NAb have been associated with survival. Furthermore, genetic variation between chickens in NAb levels has been demonstrated. To improve our understanding of the genetic variation for NAb levels in chickens we performed a genome wide association study. A population of 1,628 White Leghorn chickens was investigated. Animals were phenotyped for NAb levels using the antigen keyhole limpet hemocyanin (KLH) as model. Animals were genotyped for 15,579 single nucleotide polymorphisms (SNP). Highly significant association between SNP and NAb levels was observed on chicken chromosome 4. A single SNP was identified as the most likely candidate for this association. Identification of this candidate SNP was based on further analysis with full genome sequence genotypes and on predicted consequences of associated SNP. This candidate SNP causes a phenylalanine to leucine amino acid change in one of the leucine rich repeats in toll-like receptor 1 family member A (TLR1A). Our results suggest an important role for TLR1A in relation to NAb levels in chickens. Further study should confirm the effect of the SNP in TLR1A on NAb levels and on the (natural) immune competence of chickens. Keywords: natural antibodies, toll-like receptor, TLR1A
    A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows
    Klerk, Britt de; Emam, Mehdi ; Thompson-Crispi, Kathleen A. ; Sargolzaei, Mehdi ; Poel, Johan J. van der; Mallard, Bonnie A. - \ 2018
    BMC Genomics 19 (2018)1. - ISSN 1471-2164
    Dairy cattle - Genome-wide-association study - Immune system - Immunoglobulin class switching - Natural antibody - Vesicle trafficking

    Background: Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. NAb are poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be a key trait when evaluating an animal’s potential natural disease resistance. Variation in NAb is caused by both genetic and environmental factors. In this study genetic parameters of NAb were estimated and a genome-wide association study (GWAS) was performed to gain further understanding on the genes that are responsible for the observed genetic variation of NAb in Canadian Holsteins. Results: In total, blood samples of 1327 cows from 64 farms were studied. NAb binding to keyhole limpet hemocyanin (KLH) were determined via indirect ELISA. Immunoglobulin (Ig) isotypes, IgG and IgM, were evaluated. From the sample population, 925 cows were genotyped for 45,187 markers and each individual marker was tested to detect genetic variation in NAb levels. The relationships among animals was accounted for with genomic relationship. Results show heritabilities of 0.27 ± 0.064 (IgG) and 0.31 ± 0.065 (IgM). In total, 23 SNPs were found to be associated with IgG, but no SNPs were associated with IgM (FDR p-value < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells. Conclusions: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.

    Antigen-dependent effects of divergent selective breeding based on natural antibodies on specific humoral immune responses in chickens
    Berghof, T.V.L. ; Arts, J.A.J. ; Bovenhuis, H. ; Lammers, A. ; Poel, J.J. van der; Parmentier, H.K. - \ 2018
    Vaccine 36 (2018)11. - ISSN 0264-410X - p. 1444 - 1452.
    Breeding - Chicken - General disease resistance - Keyhole limpet hemocyanin (KLH) - Natural antibody - Specific antibody
    NAb are defined as antigen binding antibodies present without a known previous exposure to this antigen. NAb are suggested to enhance specific antibody (SpAb) responses, but consequences of different NAb levels on immunization are largely unknown. Layer chickens were divergently selected and bred for keyhole limpet hemocyanin (KLH)-binding NAb titers, resulting in a High line and a Low line. In this study, we investigated: (1) the relation of NAb levels with SpAb titers; and (2) the effect of immunization on NAb titers. The 50 highest females of the High line and the 50 lowest females of the Low line of generation 2 were intramuscularly immunized at 33 weeks of age with 1 mL phosphate buffered saline (PBS) containing one of four treatments: (1) negative control (no antigen), (2) 500 μg KLH, (3) 100 μg avian tuberculin purified protein derivative of Mycobacterium avium (PPD), or (4) 250 μg human serum albumin (HuSA). IgM and IgG titers of NAb and SpAb in plasma were determined prior to immunization and weekly for 5 weeks post immunization by indirect ELISA. In addition, antibody affinity was investigated. No differences in SpAb and NAb response against KLH and PPD were observed as a consequence of different NAb titers, but increased and prolonged SpAb and NAb titer responses against HuSA were observed for the High line compared to the Low line. Different natural antibody titers did not impair SpAb dynamics and SpAb affinity. NAb titers were not, or for only short-term, affected by immunization. We show here that NAb may enhance SpAb responses, but that this effect is antigen-dependent. We hypothesize that NAb play a role in general disease resistance through enhancement of the humoral adaptive immune response.
    Genomic Region Containing Toll-Like Receptor Genes Has a Major Impact on Total IgM Antibodies Including KLH-Binding IgM Natural Antibodies in Chickens
    Berghof, T.V.L. ; Visker, M.H.P.W. ; Arts, J.A.J. ; Parmentier, H.K. ; Poel, J.J. van der; Vereijken, A.L.J. ; Bovenhuis, H. - \ 2018
    Frontiers in Immunology 8 (2018). - ISSN 1664-3224 - 14 p.
    Natural antibodies (NAb) are antigen binding antibodies present in individuals without a previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)-binding NAb levels were previously associated with survival in chickens. This suggests that selective breeding for KLH-binding NAb may increase survival by means of improved general disease resistance. Genome-wide association studies (GWAS) were performed to identify genes underlying genetic variation in NAb levels. The studied population consisted of 1,628 adolescent layer chickens with observations for titers of KLH-binding NAb of the isotypes IgM, IgA, IgG, the total KLH-binding (IgT) NAb titers, total antibody concentrations of the isotypes IgM, IgA, IgG, and the total antibodies concentration in plasma. GWAS were performed using 57,636 single-nucleotide polymorphisms (SNP). One chromosomal region on chromosome 4 was associated with KLH-binding IgT NAb, and total IgM concentration, and especially with KLH-binding IgM NAb. The region of interest was fine mapped by imputing the region of the study population to whole genome sequence, and subsequently performing an association study using the imputed sequence variants. 16 candidate genes were identified, of which FAM114A1, Toll-like receptor 1 family member B (TLR1B), TLR1A, Krüppel-like factor 3 (KLF3) showed the strongest associations. SNP located in coding regions of the candidate genes were checked for predicted changes in protein functioning. One SNP (at 69,965,939 base pairs) received the maximum impact score from two independent prediction tools, which makes this SNP the most likely causal variant. This SNP is located in TLR1A, which suggests a fundamental role of TLR1A on regulation of IgM levels (i.e., KLH-binding IgM NAb, and total IgM concentration), or B cells biology, or both. This study contributes to increased understanding of (genetic) regulation of KLH-binding NAb levels, and total antibody concentrations.
    Reduced mortality after avian pathogenic Escherichia coli inoculation in chickens bred for high natural antibodies
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Poel, J.J. van der; Parmentier, H.K. - \ 2017
    Breeding for high natural antibodies reduces mortality after avian pathogenic Escherichia coli inoculation in chickens
    Berghof, T.V.L. ; Matthijs, Mieke ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Poel, J.J. van der; Parmentier, H.K. - \ 2017
    Chickens selected for different natural antibody levels differ in mortality to intratracheal aerial pathogenic Escherichia coli (APEC) infection
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Koning, D.B. de; Poel, J.J. van der; Parmentier, H.K. - \ 2017
    - p. 22 - 22.
    A genome-wide association of natural antibodies binding keyhole limpet hemocyanin in chickens reeals major QTL on chromosome 4 for IgM isotype
    Berghof, T.V.L. ; Parmentier, H.K. ; Arts, J.A.J. ; Hulzebosch, A.A. ; Poel, J.J. van der; Vereijken, Addie ; Visker, M.H.P.W. ; Bovenhuis, H. - \ 2017
    Chickens selected for different natural antibody levels differ in mortality to intratracheal aerial pathogenic Escherichia coli (APEC) infection
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Poel, J.J. van der; Parmentier, H.K. - \ 2016
    A genome-wide association study of natural antibodies binding keyhole limpet hemocyanin in chickens reveals major QTL on chromosome 4 for IgM isotype
    Berghof, T.V.L. ; Parmentier, H.K. ; Arts, J.A.J. ; Hulzebosch, A.A. ; Poel, J.J. van der; Vereijken, Addie ; Visker, M.H.P.W. ; Bovenhuis, H. - \ 2016
    Chickens selected for different natural antibody levels differ in mortality to intratracheal aerial pathogenic Escherichia coli (APEC) infection
    Berghof, T.V.L. ; Matthijs, M.G.R. ; Arts, J.A.J. ; Bovenhuis, H. ; Dwars, R.M. ; Koning, D.B. de; Poel, J.J. van der; Parmentier, H.K. - \ 2016
    Genetic parameters of IgM and IgG antibodies binding autoantigens in healthy chickens
    Bao, Mandy ; Bovenhuis, H. ; Nieuwland, M.G.B. ; Parmentier, H.K. ; Poel, J.J. van der - \ 2016
    Poultry Science 95 (2016)2. - ISSN 0032-5791 - p. 458 - 465.
    chicken - natural autoantibodies - autoantigen - genetic parameters
    Levels of natural antibodies (NAb) binding keyhole limpet hemocyanin (KLH) in layers were shown to be heritable and to be potential indicative parameters for survival. A proportion of NAb are directed to self-molecules, or slightly changed self-molecules (neo-epitopes), labeled as natural autoantibodies (NAAb). It is unknown whether the levels of NAAb are heritable and genetically correlated. In this paper, we estimated genetic parameters in plasma of healthy layers for IgM and IgG antibodies binding ovalbumin (OVA), myosin (MYO), cardiolipin (CAR), lysozyme (LYS), and the model antigen keyhole limpet hemocyanin (KLH). A linear animal model was used to estimate (co)variance components, heritabilities, and correlations. The estimates of heritabilities ranged from 0.10 to 0.17 for IgM, and 0.02 to 0.11 for IgG, respectively. For both IgM and IgG, high genetic correlations were observed between levels of NAAb binding autoantigens and NAb binding KLH, except for IgG binding KLH and LYS, for which a low genetic correlation was found. Low to moderate phenotypic correlations were found between NAAb and NAb. In addition, significant maternal environmental effects of 0.03, 0.07, and 0.04 were observed for IgM binding OVA, LYS, and KLH, respectively. Results from this study indicated that NAAb or NAb levels in plasma were heritable and could provide tools to identify the health status of birds.
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