Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation

BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.1<h2≤0.4) or high (h2>0.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits

Imaging and imagination: understanding the endo-lysosomal system

Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today

Unravelling the relationship between animal growth and immune response during micro-parasitic infections

Background: Both host genetic potentials for growth and disease resistance, as well as nutrition are known to affect responses of individuals challenged with micro-parasites, but their interactive effects are difficult to predict from experimental studies alone. Methodology/Principal Findings: Here, a mathematical model is proposed to explore the hypothesis that a host's response to pathogen challenge largely depends on the interaction between a host's genetic capacities for growth or disease resistance and the nutritional environment. As might be expected, the model predicts that if nutritional availability is high, hosts with higher growth capacities will also grow faster under micro-parasitic challenge, and more resistant animals will exhibit a more effective immune response. Growth capacity has little effect on immune response and resistance capacity has little effect on achieved growth. However, the influence of host genetics on phenotypic performance changes drastically if nutrient availability is scarce. In this case achieved growth and immune response depend simultaneously on both capacities for growth and disease resistance. A higher growth capacity (achieved e.g. through genetic selection) would be detrimental for the animal's ability to cope with pathogens and greater resistance may reduce growth in the short-term. Significance: Our model can thus explain contradicting outcomes of genetic selection observed in experimental studies and provides the necessary biological background for understanding the influence of selection and/or changes in the nutritional environment on phenotypic growth and immune response. © 2009 Doeschl-Wilson et al

Multi-primer target PCR for rapid identification of bovine DRB3 alleles

Multi-primer target polymerase chain reaction (MPT-PCR) is a rapid method for the identification of specific BoLA-DRB3 alleles. In a single PCR reaction, the presence of two alleles associated with increased risk, DRB3.2*23 (DRB3*2701±2703, 2705±2707) and decreased risk, DRB3.2*16 (DRB3*1501, 1502), of mastitis in Canadian Holstein can be detected. Two outer primers amplify exon 2 of DRB3. Simultaneously, two inner, allele-specific primers amplify individual alleles. Initially, 40 cows previously typed by PCR-restriction fragment length polymorphism (PCR-RFLP) were genotyped using the multi-primer approach. An additional 30 cows were first genotyped by multi-primer target PCR, then by PCR-RFLP. All animals were correctly identified and there were no false positives. This technique can readily be modified to identify other BoLA alleles of interest

PBMC transcriptomic responses to primary and secondary vaccination differ due to divergent lean growth and antibody titers in a pig model

The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals before and after two tetanus toxoid (TT) vaccinations in domestic pigs differing in lean growth (LG) and anti-TT-antibody titers (AB) parameters of performance and immunocompetence. During response to the first vaccination all animals had a general decrease in transcript abundances related to various functional pathways as measured by comparative Affymetrix microarray hybridization and Ingenuity Pathway analyses. Low-AB phenotypes had predominantly decreased immune response transcripts. Combined phenotypes high-AB/high-LG had decreased transcripts related to growth factor signaling pathways. However, during the interval after the booster vaccination, high-LG and high-AB animals responded exclusively with increased immune transcripts, such as B-cell receptor signaling and cellular immune response pathways. In addition, high-LG and low-AB animals had predominantly increased transcripts of several cellular immune response pathways. Conversely, low-LG and high-AB animals had few elevated immune transcripts and decreased transcripts related to only two nonimmune-specific pathways. In response to booster vaccination high-LG phenotypes revealed enriched transcripts related to several different immune response pathways, regardless of AB phenotype. Different from the expected impact of AB titers, divergent AB phenotypes did not reflect considerable differences between immune transcripts. However, highly significant differences observed among divergent LG phenotypes suggest the compatibility of high performance and high vaccine responses