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The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic, and phenotypic data. This methodology converts GEBVs into SNP effects. The analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2) and 1700 50K SNP genotypes. The comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21, and 25, and for FEC2 on OAR 5, 6, and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs.

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host's response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high ( n = 5) or medium ( n = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls ( n = 4), and with biased antibody-mediated (AbMR, n = 5) or cell-mediated (CMR, n = 5) adaptive immune responsiveness compared to uninfected controls ( n = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection.

We investigated the association between 157 SNPs located in 75 candidate genes involved in the immune system and proxy traits for resistance to gastrointestinal nematodes in sheep. A total of 211 lambs from eight flocks were sampled. Nematode eggs per gram were counted and classified as: (i) Strongyles, (ii) Nematodirus spp., (iii) Trichuris spp. and (iv) Marshallagia marshalli. Single- and multiple-locus models were used to test the marker-trait associations. Seven significant SNPs were identified on chromosomes OAR6, 15, 16, and 19. These findings provide insights for breeding nemarode-resistant traits in low-input production systems. General linear model, fixed and random model circulating probability unification, and Bayesian-information and linkage-disequilibrium iteratively nested keyway analyses identified a significant association between the eggs per gram of Strongyles nematodes and a specific variant of the PRLR gene., (© 2024 Stichting International Foundation for Animal Genetics.)

Gastrointestinal nematodes (GINs) can be a major constraint and global challenge to the sheep industry. These nematodes infect the small intestine and abomasum of grazing sheep, causing symptoms such as weight loss, diarrhea, hypoproteinemia, and anemia, which can lead to death. The use of anthelmintics to treat infected animals has led to GIN resistance, and excessive use of these drugs has resulted in residue traced in food and the environment. Resistance to GINs can be measured using multiple traits, including fecal egg count (FEC), Faffa Malan Chart scores, hematocrit, packed cell volume, eosinophilia, immunoglobulin (Ig), and dagginess scores. Genetic variation among animals exists, and understanding these differences can help identify genomic regions associated with resistance to GINs in sheep. Genes playing important roles in the immune system were identified in several studies in this review, such as the CFI and MUC15 genes. Results from several studies showed overlapping quantitative trait loci (QTLs) associated with multiple traits measuring resistance to GINs, mainly FEC. The discovery of genomic regions, positional candidate genes, and QTLs associated with resistance to GINs can help increase and accelerate genetic gains in sheep breeding programs and reveal the genetic basis and biological mechanisms underlying this trait.

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10-SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha© (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein-coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, the association between PAPPA2 coding variants and gastrointestinal (GI) nematode fecal egg count (FEC) score in adult Turkish sheep was investigated. For this purpose, the FEC score was determined in adult sheep from six breeds: Karacabey Merino (n = 137), Kivircik (n = 116), Cine capari (n = 109), Karakacan (n = 102), Imroz (n = 73), and Chios (n = 50). Sheep were classified as shedders or non-shedders within breeds and flocks. The first group was the fecal egg shedders (> 50 per gram of feces), and the second group was the no fecal egg shedders (≤ 50 per gram of feces). The exon 1, exon 2, exon 5, exon 7, and a part of 5'UTR of the ovine PAPPA2 gene were genotyped by Sanger sequencing of these two groups. Fourteen synonymous and three non-synonymous single-nucleotide polymorphisms (SNPs) were found. The non-synonymous SNPs, D109N, D391H, and L409R variants, are reported for the first time. Two haplotype blocks were constructed on exon 2 and exon 7. The specific haplotype, C 391 G 424 G 449 T 473 C 515 A 542 on the exon 2 that carries the 391H variant, was tested against four other common haplotypes. Our results indicate that C 391 G 424 G 449 T 473 C 515 A 542 haplotype was significantly associated with fecal egg shedding status in adult Turkish sheep (p-value, 0.044)., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Due to progressing anthelmintic resistance of gastrointestinal nematodes (GIN), supportive measures are needed to control these parasites. In sheep, it has been shown that selection towards an increased nematode resistance is feasible and that faecal egg count (FEC) is the generally acknowledged trait for selection. However, a selection based on FEC would come with certain costs, therefore auxiliary, cheaper resistance traits would be most welcome. FAMACHA©, a colour classification of the eyelid, usually used to determine the manifestation of an infection with Haemonchus contortus, could serve as such. Therefore, we collected FAMACHA©, packed cell volume (PVC) and FEC phenotypes of approx. 1150 naturally infected Lacaune ewes on 15 commercial farms in Switzerland. The Haemonchus-proportion was determined on farm level. Phenotypic correlations of FEC and FAMACHA© as well as FAMACHA© and PCV were 0.25 (SE 0.03) and -0.35 (SE 0.08), respectively, and correspond well with the results of other studies. A multi-trait animal model was applied to estimate genetic parameters with FEC, FAMACHA©, PVC and milk yield as dependent variables. The heritabilities of FEC, FAMACHA©, PCV and milk yield were estimated to be moderate with values of 0.33 (SE 0.08), 0.30 (SE 0.08), 0.36 (SE 0.08) and 0.34 (SE 0.08), respectively. The genetic correlations between FEC and FAMACHA© and between FEC and PCV were estimated to be close to zero with values of 0.03 (SE 0.22) and 0.01 (SE 0.21), respectively. The average Haemonchus-proportion compared to other GIN was found to be 43%. The FAMACHA© classification of the Lacaune ewes seems to indicate a rather high worm challenge, with 38, 14 and 2% of observations classified to scores 3, 4 and 5, respectively. However, the worm challenge according to FEC was moderate. It has been suggested that the genetic correlation between FAMACHA© and FEC is more pronounced when FEC was high. It could therefore be that the lack of genetic correlation was due to an insufficient worm challenge, even though the Lacaune were grazing at least 70 days before phenotyping. The genetic correlation between FEC and milk yield was estimated to be 0.07 (SE 0.22, slightly unfavourable). We conclude that if FEC is used as trait, the Lacaune could be selected for lower susceptibility towards nematode infection. The use of FAMACHA© as an auxiliary trait for FEC is not feasible, due to an inexistent genetic correlation between these two traits., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens. However, anthelmintic resistance (AR) is increasing, and little is known about the molecular and genetic causes of resistance for most drugs. The free-living roundworm Caenorhabditis elegans has proven to be a tractable model to understand AR, where studies have led to the identification of molecular targets of all major anthelmintic drug classes. Here, we used genetically diverse C. elegans strains to perform dose-response analyses across 26 anthelmintic drugs that represent the three major anthelmintic drug classes (benzimidazoles, macrocyclic lactones, and nicotinic acetylcholine receptor agonists) in addition to seven other anthelmintic classes. First, we found that C. elegans strains displayed similar anthelmintic responses within drug classes and significant variation across drug classes. Next, we compared the effective concentration estimates to induce a 10% maximal response (EC10) and slope estimates of each dose-response curve of each strain to the laboratory reference strain, which enabled the identification of anthelmintics with population-wide differences to understand how genetics contribute to AR. Because genetically diverse strains displayed differential susceptibilities within and across anthelmintics, we show that C. elegans is a useful model for screening potential nematicides before applications to helminths. Third, we quantified the levels of anthelmintic response variation caused by genetic differences among individuals (heritability) to each drug and observed a significant correlation between exposure closest to the EC10 and the exposure that exhibited the most heritable responses. These results suggest drugs to prioritize in genome-wide association studies, which will enable the identification of AR genes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shaver et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastrointestinal nematode (GINs) infections are one of the causative agents of health and economic issues in sheep production systems worldwide. Considerable genetic variations in resistance or susceptibility in different sheep breeds are documented, but published results are conflicting. Recent advances obtained by high-throughput technologies such as commercial SNP chips, whole-genome sequencing, or whole transcriptome profiling provide new insights into breeding for host resistance or nematode control at the genetic levels. This study aimed to identify potential biomarkers associated with the resistance to ovine GINs through a network analysis approach. Comprehensive gene and protein interaction networks were reconstructed for candidate genes involved in the most related immune pathways associated with resistance to ovine GINs using data mining from literature. Generally, 30 genes including CD53, CHIA, RELN, HRH1, EPS15, LRP8, ATP2B1, IL4, IL5, IL13, IL2RA, IL23R, TNFα, IFNγ, TBX21, SH3RF1, HERC2, PTPN1, BIN1, HERC5, C3AR1, NOS2, STAT5B, STAT4, CCL1, CCL8, VIL1, CXCR1, CXCR2, and CXCR4 located on chromosomes 1, 2, 3, 4, 5, 6, 11, 13, 19, and 20 have been found as containing effective regions with the most related pathways to nematode infections. The results obtained by network analysis showed two functional modules, belonging to the interleukins family (IL4, IL5, IL13, IL23R, and IL2RA) and chemokine receptors or ligands family (CXCR1, CXCR2, CXCR4, CCL1, and CCL8). Interleukins are a group of cytokines that are expressed by white blood cells with a major role in the immune system. Chemokines are also a family of chemoattractant cytokines which play a vital role in cell migration that influence the immune system by a process known as chemotaxis. The results provide useful information for the functional annotation of candidate genes related to parasite resistance and add new information towards a consensus on quantitative trait loci (QTLs) related to the incidence of nematode infections., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The developing brain is particularly vulnerable to factors including maternal infection during pregnancy. Establishment of neural networks critical for memory and cognition begins during the perinatal period, when Heligmosomoides bakeri, a gastrointestinal (GI) nematode restricted to the maternal mouse intestine, has been shown to upregulate expression of long-term potentiation genes in the young rodent pup brain. We explored the impact of maternal infection during pregnancy and early lactation on the spatial behavior of uninfected male and female juvenile mice. Pre-weaned pups of H. bakeri infected dams exhibited less exploratory behaviour compared to pups of uninfected dams on postnatal day (PD) 16 but not PD 17, possibly reflecting a transient fear of an unfamiliar environment and/or a brief neurodevelopmental delay. Our two spatial memory tests show for the first time an enhancement of spatial memory in response to maternal nematode infection regardless of pup sex. At PD 17, pups of infected dams expressed object location memories after 3 h in the Object Location Test whereas offspring of uninfected mothers did not. In addition, at PD 34, juveniles of infected mothers retained their ability to find the escape hole in the Barnes Maze Test for one week whereas offspring from uninfected mothers did not. This finding is even more striking given that spatial memory was positively associated with pup length, yet this maternal infection impaired linear growth of pups. Thus, the positive impact of maternal infection on spatial memory countered any impairment associated with the shorter length of the pups. Overall, these novel findings indicate that a maternal GI nematode infection during pregnancy and lactation positively influences the spatial memory of uninfected juvenile offspring with potential fitness implications for the next generation., (© 2022. The Author(s).)

Infection caused by gastrointestinal nematodes is an important issue for animal health and production. Controlling worm infections improves the sustainability of the sheep industry. Genetic selection of animals that are resistant to gastrointestinal nematodes is another strategy to render sheep production more sustainable by decreasing the use of anthelmintics. The aims of this study were (1) to explore the additive-genetic pattern of EBVs for Famacha© (FAM), packed-cell volume (PVC), and fecal egg counts (FEC) of Santa Ines sheep, (2) to propose a classification of animals that are resistant, resilient and susceptible to gastrointestinal nematodes based on their additive-genetic patterns, and (3) to identify the most suitable animals for selection based on their genetic pattern. A dataset of 2,241 records from 747 animals was used to predict the breeding values for indicator traits of resistance to gastrointestinal nematodes with THRGIBBS1F90 and to carry out cluster analyses was used R software. Three clusters of animals were found in the population using hierarchical cluster analysis of the breeding values for FAM, PCV and FEC. Each cluster was characterized by different additive-genetic patterns identified by k-means non-hierarchical cluster analysis. Among a total of 747 animals, 196 were classified as resistant, 288 as resilient, and 263 as susceptible. Cluster analysis is a valuable tool for data screening that permits to evaluate only selection candidates based on their additive-genetic pattern for gastrointestinal nematode resistance. EBVs for FEC were decisive to divide the population into resilient, resistant and susceptible animals. It is also important to include the EBVs for PCV and FAM to adequately distinguish resistant from resilient animals. Finally, the resistant cluster consisted of the most desirable animals to be used as selection candidates in order to genetically improve resistance to infection with gastrointestinal nematodes. This cluster contained animals with the most appropriate additive-genetic pattern to achieve the breeding goal, with positive breeding values for PCV and negative breeding values for FAM and FEC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intestinal nematode infections common during pregnancy have recently been shown to have impacts that extend to their uninfected offspring including altered brain gene expression. If maternal immune signals reach the neonatal brain, they might alter neuroimmune development. We explored expression of genes associated with four distinct types of T cells (Th1, Th2, Th17, Treg) and with leukocyte transendothelial migration and endocytosis transport across the blood-brain barrier (BBB) in the postnatal brain of offspring of nematode-infected mice, through secondary analysis of a whole brain gene expression database. Th1/Th17 expression was lowered by maternal infection as evidenced by down-regulated expression of IL1β, Th1 receptors and related proteins, and of IL22 and several Th17 genes associated with immunopathology. In contrast, Th2/Treg related pathways were upregulated as shown by higher expression of IL4 and TGF-β family genes. Maternal infection also upregulated expression of pathways and integrin genes involved in transport of leukocytes in between endothelial cells but downregulated endosome vesicle formation related genes that are necessary for endocytosis of immunoglobulins across the BBB. Taken together, pup brain gene expression indicates that maternal nematode infection enhanced movement of leukocytes across the neonatal BBB and promoted a Th2/Treg environment that presumably minimizes the proinflammatory Th1 response in the pup brain., (© 2021. The Author(s).)

The entomopathogenic nematodes Heterorhabditis and Steinernema form mutualistic complexes with Gram-negative bacteria. These insect parasites have emerged as excellent research tools for studying nematode pathogenicity and elucidating the features that allow them to persist and multiply within the host. A better understanding of the molecular mechanisms of nematode infection and host antinematode processes will lead to the development of novel means for parasitic nematode control. Recent work has demonstrated the power of using the Drosophila infection model to identify novel parasitic nematode infection factors and elucidate the genetic and functional bases of host antinematode defense. Here, we aim to highlight the recent advances and address their contribution to the development of novel means for parasitic nematode control., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pine wood nematode (PWN) causes serious diseases in conifers, especially pine species. To investigate the transcriptomic profiles of genes involved in pine-PWN interactions, two different pine species, namely, Pinus thunbergii and P. massoniana , were selected for this study. Weighted gene coexpression network analysis (WGCNA) was used to determine the relationship between changes in gene expression and the PWN population after PWN infection. PWN infection negatively affects the expression of most genes in pine trees, including plant defense-related genes such as genes related to plant hormone signal transduction, plant-pathogen interactions, and the MAPK signaling pathway in plants. However, the expression of chalcone synthase genes and their related genes were proportional to the changes in nematode populations, and chalcone synthase genes were dominant within the coexpression module enriched by genes highly correlated with the nematode population. Many genes that were closely related to chalcone synthase genes in the module were related to flavonoid biosynthesis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis. Pine trees could actively adjust their defense strategies in response to changes in the number of invasive PWNs, but the sustained expression of chalcone synthase genes should play an important role in the inhibition of PWN infection.

Scrapie is a transmissible spongiform encephalopathy caused by prions and leads to neurodegeneration in the Central Nervous System (CNS) of sheep and goats. Genetic resistance/susceptibility to scrapie is well studied and it is known that the variations of 136th, 154th and 171st codons at the ovine PRNP gene have a major effect on the development of the disease. Many studies demonstrated that selection for PRNP genotypes has not influenced other performance traits, nevertheless, there is a knowledge gap about the possible link between the PRNP gene and the status of the other important diseases that affect the sheep population worldwide. In the present study, we tested whether there is an association between scrapie-related PRNP genotypes and fecal egg count (FEC) of gastrointestinal nematodes in seven adult Turkish sheep breeds. For this purpose, FEC scores of studied sheep ( n  = 253) were determined and the same animals were genotyped for the PRNP gene. Finally, an association analysis was performed for scrapie resistant (ARR), susceptible (VRQ), and wild-type (ARQ) haplotypes. Based on our statistical analysis, it is concluded that PRNP genotypes have no positive or negative effect on the FEC scores of adult sheep.

Gastrointestinal nematode (GIN) infections have negative impacts on animal health, welfare and production. Information from molecular studies can highlight the underlying genetic mechanisms that enhance host resistance to GIN. However, such information often lacks for traditionally managed indigenous livestock. Here, we analysed 600 K single nucleotide polymorphism genotypes of GIN infected and non-infected traditionally managed autochthonous Tunisian sheep grazing communal natural pastures. Population structure analysis did not find genetic differentiation that is consistent with infection status. However, by contrasting the infected versus non-infected cohorts using ROH, LR-GWAS, F ST and XP-EHH, we identified 35 candidate regions that overlapped between at least two methods. Nineteen regions harboured QTLs for parasite resistance, immune capacity and disease susceptibility and, ten regions harboured QTLs for production (growth) and meat and carcass (fatness and anatomy) traits. The analysis also revealed candidate regions spanning genes enhancing innate immune defence (SLC22A4, SLC22A5, IL-4, IL-13), intestinal wound healing/repair (IL-4, VIL1, CXCR1, CXCR2) and GIN expulsion (IL-4, IL-13). Our results suggest that traditionally managed indigenous sheep have evolved multiple strategies that evoke and enhance GIN resistance and developmental stability. They confirm the importance of obtaining information from indigenous sheep to investigate genomic regions of functional significance in understanding the architecture of GIN resistance.

Gastrointestinal parasitism is a global problem for grazing ruminants which can be addressed in a sustainable way through breeding animals to be more resistant to disease. This study estimates the genetic parameters of common and new disease phenotypes associated with natural nematode and coccidian infection in Scottish Blackface sheep to underpin future genetic improvement strategies for parasite control. Data on faecal egg counts (FEC) from different species of strongyle parasites and faecal oocyst counts (FOC) from coccidian parasites were collected on 3-month-old lambs together with a faecal soiling score in the breech area dagginess (DAG) and live weight (LWT). Faecal count data were obtained for Strongyles (FEC S ), Nematodirus (FEC N ) and Coccidia (FOC). Data from 3 731 lambs sampled between 2011 and 2017 were included. Faecal egg counts and DAG records were log-transformed prior to analysis. Data were analysed using linear mixed models. Average age at sampling was 92 days with a mean LWT of 24.5 kg. Faecal soiling was not evident in 69% of lambs. Coccidia were the most prevalent parasite (99.5%), while Strongyles and Nematodirus had a prevalence of 95.4% and 72.7%, respectively. Heritability estimates (±SE) were 0.16 ± 0.03, 0.17 ± 0.03, 0.09 ± 0.03, 0.09 ± 0.03 and 0.33 ± 0.04 for FEC S , FEC N , FOC, DAG and LWT, respectively. Strongyles faecal egg count had a strong and positive genetic correlation with FEC N (0.74 ± 0.09) and a moderate positive correlation with FOC (0.39 ± 0.15) while DAG was negatively genetically correlated with LWT (-0.33 ± 0.15). The significant positive genetic correlations between FEC S , FEC N and FOC at 3 months of age show that co-selection of sheep for resistance to these different parasites is feasible. Selection for increased resistance to parasite infection is not expected to adversely affect live BW, as no significant antagonistic genetic correlations were found between LWT and FEC. There were significant antagonistic phenotypic and genetic relationships between DAG and LWT being -0.19 ± 0.02 and -0.33 ± 0.15, respectively, indicating that the expression of the manifestation of disease in lambs may be a more meaningful indicator of the impact of parasite burden on productivity., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Gastrointestinal nematodes (GIN) are an important constraint in small ruminant production. Genetic selection for resistant animals is a potential sustainable control strategy. Advances in molecular genetics have led to the identification of several molecular genetic markers associated with genes affecting economic relevant traits. In this study, the variants in the genome of Creole goats resistant or susceptible to GIN were discovered from RNA-sequencing. We identified SNPs, insertions and deletions that distinguish the two genotypes, resistant and susceptible and we characterized these variants through functional analysis. The T cell receptor signalling pathway was one of the top significant pathways that distinguish the resistant from the susceptible genotype with 78% of the genes involved in this pathway showing genomic variants. These genomic variants are expected to provide useful resources especially for molecular breeding for GIN resistance in goats., Competing Interests: The authors declare no competing interests.

Insects in nature interact with a wide variety of microbial enemies including nematodes. These include entomopathogenic nematodes that contain mutualistic bacteria and together are able to infect a broad range of insects in order to complete their life cycle and multiply, filarial nematodes which are vectored by mosquitoes, and other parasitic nematodes. Entomopathogenic nematodes are commonly used in biological control practices and they form excellent research tools for understanding the genetic and functional bases of nematode pathogenicity and insect anti-nematode immunity. In addition, clarifying the mechanism of transmission of filarial nematodes by mosquitoes is critical for devising strategies to reduce disease transmission in humans. In all cases and in order to achieve these goals, it is vital to determine the number and type of insect host genes which are differentially regulated during infection and encode factors with anti-nematode properties. In this respect, the use of transcriptomic approaches has proven a key step for the identification of insect molecules with anti-nematode activity. Here, we review the progress in the field of transcriptomics that deals with the insect response to nematode infection. This information is important because it will expose conserved pathways of anti-nematode immunity in humans.

Trifoliate orange (Poncirus trifoliata), a deciduous close relative of evergreen Citrus, has important traits for citrus production, including tolerance/resistance to citrus greening disease (Huanglongbing, HLB) and other major diseases, and cold tolerance. It has been one of the most important rootstocks, and one of the most valuable sources of resistance and tolerance genes for citrus. Here we present a high-quality, chromosome-scale genome assembly of P. trifoliata. The 264.9-Mb assembly contains nine chromosomal pseudomolecules with 25 538 protein-coding genes, covering 97.2% of the estimated gene space. Comparative analyses of P. trifoliata and nine Citrus genomes revealed 605 species-specific genes and six rapidly evolving gene families in the P. trifoliata genome. Poncirus trifoliata has evolved specific adaptation in the C-repeat/DREB binding factor (CBF)-dependent and CBF-independent cold signaling pathways to tolerate cold. We identified candidate genes within quantitative trait loci for HLB tolerance, and at the loci for resistance to citrus tristeza virus and citrus nematode. Genetic diversity analysis of Poncirus accessions and Poncirus/Citrus hybrids shows a narrow genetic base in the US germplasm collection, and points to the importance of collecting and preserving more natural genetic variation. Two phenotypically divergent Poncirus accessions are found to be clonally related, supporting a previous conjecture that dwarf Flying Dragon originated as a mutant of a non-dwarfing type. The high-quality genome reveals features and evolutionary insights of Poncirus, and it will serve as a valuable resource for genetic, genomic and molecular research and manipulation in citrus., (© 2020 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

In plant immune responses, reactive oxygen species (ROS) act as signaling molecules that activate defense pathways against pathogens, especially following resistance (R) gene-mediated pathogen recognition. Glutathione (GSH), an antioxidant and redox regulator, participates in the removal of hydrogen peroxide (H 2 O 2 ). However, the mechanism of GSH-mediated H 2 O 2 generation in soybeans ( Glycine max (L.) Merr.) that are resistant to the soybean cyst nematode (SCN; Heterodera glycines Ichinohe) remains unclear. To elucidate this underlying relationship, the feeding of race 3 of H. glycines with resistant cultivars, Peking and PI88788, was compared with that on a susceptible soybean cultivar, Williams 82. After 5, 10, and 15 days of SCN infection, we quantified γ-glutamylcysteine (γ-EC) and (homo)glutathione ((h)GSH), and a gene expression analysis showed that GSH metabolism in resistant cultivars differed from that in susceptible soybean roots. ROS accumulation was examined both in resistant and susceptible roots upon SCN infection. The time of intense ROS generation was related to the differences of resistance mechanisms in Peking and PI88788. ROS accumulation that was caused by the (h)GSH depletion-arrested nematode development in susceptible Williams 82. These results suggest that (h)GSH metabolism in resistant soybeans plays a key role in the regulation of ROS-generated signals, leading to resistance against nematodes.

Beneficial microorganisms are generally known to activate plant defense against biotic challenges. However, the molecular mechanisms by which activated plants react more rapidly and actively to pests remain still largely unclear. Tomato plants pre-treated with a mixture of beneficial bio-control agents (BCAs), as soil-drenches, were less sensitive to infection of the root-knot nematode (RKN) Meloidogyne incognita. To unravel the molecular mechanisms of this induced resistance against RKNs, we used qRT-PCR to monitor the expression, in tomato roots and leaves, of 6 key defense genes. Gene transcripts were detected until the 12th day after BCA treatment(3, 7, 8, 12 dpt) and3 and 7 days after nematode inoculation of pre-treated plants. Early after BCA treatment, the salicylic acid (SA)-dependent pathogenesis related gene (PR-gene), PR-1b, marker of the systemic acquired resistance (SAR), was systemically over-expressed. Another PR-gene, PR-5, was over-expressed at later stages of BCA-plant interaction, and only in roots. Activation of defense against RKNs was attested by the early up-regulation of 4 genes (PR-1, PR-3, PR-5, ACO) in pre-treated plants after inoculation. Conversely, the expression of the JA/ET-dependent gene JERF3 did not increase after nematode inoculation in primed plants. A catalase gene (CAT)was highly over-expressed by nematode infection, however, this over-expression was annulled at the earliest stages or limited at the later stages of infection toBCA-treated roots. Enzyme activities, such as glucanase and endochitinase, were enhanced in roots of pre-treated inoculated plants with respect to plants left not inoculated as a control. These findings indicate that BCA interaction with roots primes plants against RKNs. BCA-mediated immunity seems to rely on SA-mediated SAR and to be associated with both the activation of chitinase and glucanase enzyme activities and the inhibition of the plant antioxidant enzyme system. Immunity is triggered at the penetration and movements inside the roots of the invading nematode juveniles but probably acts at the feeding site building stage of nematode infection., Competing Interests: The authors have declared that no competing interests exist.

Gastrointestinal nematodes (GIN) are a major constraint for small ruminant production. Due to the rise of anthelmintic resistance throughout the world, alternative control strategies are needed. The development of GIN resistance breeding programs is a promising strategy. However, a better understanding of the mechanisms underlying genetic resistance might lead to more effective breeding programmes. In this study, we compare transcriptome profiling of abomasal mucosa and lymph node tissues from non-infected, resistant and susceptible infected Creole goats using RNA-sequencing. A total of 24 kids, 12 susceptible and 12 GIN resistant based on the estimated breeding value, were infected twice with 10,000 L3 Haemonchus contortus. Physiological and parasitological parameters were monitored during infection. Seven weeks after the second infection, extreme kids (n = 6 resistant and 6 susceptible), chosen on the basis of the fecal egg counts (FEC), and 3 uninfected control animals were slaughtered. Susceptible kids had significantly higher FEC compared with resistant kids during the second infection with no differences in worm burden, male and female worm count or establishment rate. A higher number of differentially expressed genes (DEG) were identified in infected compared with non-infected animals in both abomasal mucosa (792 DEG) and lymph nodes (1726 DEG). There were fewer DEG in resistant versus susceptible groups (342 and 450 DEG, in abomasal mucosa and lymph nodes respectively). 'Cell cycle' and 'cell death and survival' were the main identified networks in mucosal tissue when comparing infected versus non-infected kids. Antigen processing and presentation of peptide antigen via major histocompatibility complex class I were in the top biological functions for the DEG identified in lymph nodes. The TGFβ1 gene was one of the top 5 upstream DEG in mucosal tissue. Our results are one of the fist investigating differences in the expression profile induced by GIN infection in goats., Competing Interests: The authors have declared that no competing interests exist.

Milk somatic cell count (SCC) is commonly higher in goats than in cattle and sheep. Furthermore, the ability of milk SCC to predict mastitis is considered lower in goats than in cattle and sheep, and the relevance of somatic cell score (SCS)-based selection in this species has been questioned. To address this issue, we created 2 divergent lines of Alpine goats using artificially inseminated bucks with extreme estimated breeding values for SCS. A total of 287 goats, 158 in high- and 129 in low-SCS lines, were scrutinized for mastitis infections. We subjected 2,688 milk samples to conventional bacteriological analyses on agarose and bacterial counts were estimated for positive samples. The SCS, milk yield, fat content, and protein content were recorded every 3 wk. Clinical mastitis was systematically noted. A subset of 40 goats (20 from each line) was subsequently challenged with Haemonchus contortus and monitored for anemia (blood packed cell volume) and fecal egg counts to see if SCS-based selection had an indirect effect on resistance to gastrointestinal nematodes. Milk production traits, including milk quantity, fat content, and protein content, were similar in both goat lines. In contrast, the raw milk SCC almost doubled between the lines, with 1,542,000 versus 855,000 cells/mL in the high- and low-SCS lines, respectively. The difference in breeding value for SCS between lines was 1.65 genetic standard deviation equivalents. The Staphylococcus spp. most frequently isolated from milk were S. xylosus, S. caprae, S. epidermidis, and S. aureus. The frequency of positive bacteriology samples was significantly higher in the high-SCS line (49%) than in the low-SCS line (33%). The highest odds ratio was 3.49 (95% confidence interval: 11.95-6.25) for S. aureus. The distribution of bacterial species in positive samples between lines was comparable. The average quantity of bacteria in positive samples was also significantly higher in high-SCS goats (69 ± 80 growing colonies) than in low-SCS goats (38 ± 62 growing colonies). Clinical cases were rare and equally distributed between high- (n = 4; 2.5%) and low-SCS (n = 3; 2.3%) lines. Furthermore, the larger the amounts of bacteria in milk the higher the SCS level. Conversely, goats with repeatedly culture-negative udders exhibited the lowest SCC levels, with an average of below 300,000 cells/mL. We therefore confirmed that SCS is a relevant predictor of intramammary infection and hygienic quality of milk in goats and can be used for prophylactic purposes. After challenge with H. contortus, goats were anemic with high fecal egg counts but we found no difference between the genetic lines. This result provides initial evidence that resistance to mastitis or to gastrointestinal nematodes infections is under independent genetic regulation. Altogether, this monitoring of the goat lines indicated that SCS-based selection helps to improve udder health by decreasing milk cell counts and reducing the incidence of infection and related bacterial shedding in milk. Selection for low SCC should not affect a goat's ability to cope with gastrointestinal nematodes., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Establishment of neural networks critical for memory and cognition begins during the perinatal period but studies on the impact of maternal infection are limited. Using a nematode parasite that remains in the maternal intestine, we tested our hypothesis that maternal infection during pregnancy and early lactation would alter perinatal brain gene expression, and that the anti-inflammatory nature of this parasite would promote synaptic plasticity and long-term potentiation. Brain gene expression was largely unaffected two days after birth, but in seven-day old pups, long-term potentiation and four related pathways essential for the development of synaptic plasticity, cognition and memory were up-regulated in pups of infected dams. Interestingly, our data suggest that a lowering of Th1 inflammatory processes may underscore the apparent beneficial impact of maternal intestinal infection on long-term potentiation.

Background: Parasite infections can have substantial impacts on population dynamics and are accordingly a key challenge for wild population management. Here we studied genetic mechanisms driving parasite resistance in a large herbivore through a comprehensive approach combining measurements of neutral (16 microsatellites) and adaptive (MHC DRB1 exon 2) genetic diversity and two types of gastrointestinal parasites (nematodes and coccidia)., Results: While accounting for other extrinsic and intrinsic predictors known to impact parasite load, we show that both neutral genetic diversity and DRB1 are associated with resistance to gastrointestinal nematodes. Intermediate levels of multi-locus heterozygosity maximized nematodes resistance, suggesting that both in- and outbreeding depression might occur in the population. DRB1 heterozygosity and specific alleles effects were detected, suggesting the occurrence of heterozygote advantage, rare-allele effects and/or fluctuating selection. On the contrary, no association was detected between genetic diversity and resistance to coccidia, indicating that different parasite classes are impacted by different genetic drivers., Conclusions: This study provides important insights for large herbivores and wild sheep pathogen management, and in particular suggests that factors likely to impact genetic diversity and allelic frequencies, including global changes, are also expected to impact parasite resistance.

Brugia malayi is a nematode that causes human lymphatic filariasis. Previously, we showed that mannose-binding lectin (MBL)-A is necessary for clearance of B. malayi microfilariae in mice and presence of MBL-A is linked with maximal levels of parasite-specific IgM. Common human MBL gene polymorphisms result in low MBL expression and lead to recurring bacterial infections. Furthermore, these low-expressing human MBL polymorphisms result in greatly increased susceptibility to lymphatic filarial infection. Indeed, gain of new filarial infections over a 30-year period are 10-fold higher in people with low, compared to high, MBL-expression phenotypes. Human MBL closely resembles mouse MBL-C, rather than MBL-A; therefore, we examined the role of mouse MBL-C in clearance of microfilariae. Absence of MBL-C alone, or both MBL-A and -C, resulted in delayed clearance of microfilariae and reduced parasite-specific IgM in mice. There were few profound changes in B cell sub-populations or in the ability of MBL-deficient mice to respond to T-dependent or T-independent antigens. However, absence of MBL-A and/or MBL-C resulted in reduced IgM to phosphorylcholine, a constituent of filarial and bacterial antigens, suggesting that inability to form proficient antibody responses to this moiety leads to lack of microfilarial clearance and overall susceptibility to filariasis., (© 2018 Australasian Society for Immunology Inc.)

Plant parasitic nematodes must be able to locate and feed from their host in order to survive. Here we show that Pratylenchus coffeae regulates the expression of selected cell-wall degrading enzyme genes relative to the abundance of substrate in root exudates, thereby tailoring gene expression for root entry of the immediate host. The concentration of cellulose or xylan within the exudate determined the level of β-1,4-endoglucanase (Pc-eng-1) and β-1,4-endoxylanase (Pc-xyl) upregulation respectively. Treatment of P. coffeae with cellulose or xylan or with root exudates deficient in cellulose or xylan conferred a specific gene expression response of Pc-eng-1 or Pc-xyl respectively with no effect on expression of another cell wall degrading enzyme gene, a pectate lyase (Pc-pel). RNA interference confirmed the importance of regulating these genes as lowered transcript levels reduced root penetration by the nematode. Gene expression in this plant parasitic nematode is therefore influenced, in a host-specific manner, by cell wall components that are either secreted by the plant or released by degradation of root tissue. Transcriptional plasticity may have evolved as an adaptation for host recognition and increased root invasion by this polyphagous species., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: James McCarthy is employed by a commercial company (Nestle S.A).

The objective of the study was to evaluate phenotypic resistance against gastrointestinal nematodes in Blackbelly, Pelibuey and Katahdin ewes before pregnancy in the humid tropics of Mexico. Individual faecal and blood samples were taken in 59 Pelibuey, 69 Blackbelly and 73 Katahdin ewes. The egg count per gram of faeces (EPG) of gastrointestinal nematodes (GINs) was determined. The percentage of packed cell volume (PCV) and body condition score (BCS) of each animal were also recorded. The ewes were segregated as susceptible, intermediate or resistant based on the EPG using the quartile method. The data were analysed using the general linear method, and the means between breeds were compared by Tukey's test. The relationships between the EPG, PCV and BCS were evaluated by Spearman correlation. The Katahdin ewes showed the highest EPG counts (3613.6 ± 5649) compared to the Blackbelly and Pelibuey ewes (576.1 ± 1009 and 56.8 ± 187, respectively, P < 0.01). The PCV values between breeds were similar (P > 0.05). The susceptible ewes had the highest EPG counts and the lowest PCV percentage (5069 ± 6404 and 22.8% ± 8.1% respectively) compared to the resistant ewes (P < 0.01). A higher percentage of Katahdin ewes were susceptible compared to the other breeds (P < 0.05). The main GIN species were Haemonchus contortus, Trichostrongylus colubriformis and Cooperia curticei. In conclusion, Katahdin ewes showed susceptibility to GIN compared to Blackbelly and Pelibuey ewes before the pregnancy period in the humid tropics of Mexico.

A 17-month-old boy from Vancouver, Canada, presented with a 5-day history of progressive somnolence, ataxia, and torticollis. Additional investigations revealed eosinophilic encephalitis with deep white matter changes on MR imaging. On day 13, serology came back positive for Baylisascaris procyonis antibodies. While prophylaxis after ingestion of soil or materials potentially contaminated with raccoon feces can prevent baylisascariasis, timely treatment can sometimes alter a disastrous outcome. Populations of infected raccoons are propagating globally, but cases of Baylisascaris neural larva migrans have so far only been reported from North America., Competing Interests: The authors declare no conflicts of interest.

The objective of this study was to explore the sensitivity of breeding values for growth rate and worm egg count (WEC, cube root transformed) to environmental worm burden, measured as the average WEC for each contemporary group (CGWEC). Growth rate and WEC were measured on 7,818 naturally infected Merino lambs in eight flocks across Australia, linked through common use of AI sires. Through bivariate analysis, genetic correlations of 0.55 ± 0.23 and 0.30 ± 0.16 were found for growth rate and WEC between low and high CGWEC, respectively. In a second analysis, breeding values for growth rate and WEC were regressed on CGWEC with a random regression model. The heritability for growth rate varied from 0.23 to 0.16 from low to high CGWEC, and the heritability for WEC varied from 0.25 to 0.36. Results suggest that breeding values for both growth rate and WEC are sensitive to environmental worm burden. Animals expressed less genetic variation for growth rate and more genetic variation for WEC in high CGWEC than in low CGWEC. This form of genotype-by-environment interaction should therefore be considered in genetic evaluation of both growth rate and WEC, to increase the efficiency of selection for animals that are more parasite resistant and more resilient to environmental worm challenge., (© 2018 The Authors. Journal of Animal Breeding and Genetics Published by Blackwell Verlag GmbH.)

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region-wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12., (© 2018 Stichting International Foundation for Animal Genetics.)

Breeding sheep for enhanced resistance to gastrointestinal parasites is a promising strategy to limit the use of anthelmintics due to the now widespread resistance of parasites to these molecules. This paper reports the genetic parameters estimated for parasite resistance and resilience traits in the Blond-faced Manech dairy sheep breed and the putative impacts of the selection for resistance to gastrointestinal nematodes (GIN) on farms. Two datasets were used. First, the rams of the selection scheme were artificially infected twice with L3 Haemonchus contortus larvae. Faecal egg counts (FEC) and packed cell volume (PCV) loss were measured 30 days after each infection. Secondly, the FEC, PCV and body condition score (BCS) (1-6 measures per ewe) of naturally infected ewes on farms were measured in the spring, summer and autumn over a two-year period. Genetic parameters were estimated for each dataset independently but also globally based on the pedigree connections between the two datasets. For the experimentally infected sires, the FEC following the second infection was moderately heritable (heritability: 0.35) and strongly correlated with FEC after the first infection (genetic correlation: 0.92). For the naturally infected ewes, FEC was also heritable (0.18). Using the two datasets together, a genetic correlation of 0.56-0.71 was estimated between the FEC values of the experimentally infected rams and naturally infected ewes. Consequently, the genetic variability of parasite resistance is similar whatever the physiological status (males or milking/pregnant ewes) and the infection conditions (experimental infection with one parasite or natural infection with several parasites). In practice, when the sire population is divided into two groups based on their genetic value, the FEC of the ewes born to the 50% most resistant sires is half that of the ewes born to the 50% most susceptible sires. Our study shows the feasibility and efficiency of genetic selection for parasitism resistance based on the sires' FEC records to improve parasite resistance in naturally grazing ewes. For breed improvement, and to increase the selection pressure on parasite resistance, it seems more appropriate to measure FEC values on rams after experimental infection rather than on ewes in natural infection conditions because this limits the number and standardizes the conditions of FEC measurements., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The rate of glucose metabolism has been shown to be correlated to glucose uptake in swimbladder gas gland cells. Therefore, it is assumed that in the European eel silvering, i.e., the preparation of the eel for the spawning migration to the Sargasso Sea, coincides with an enhanced capacity for glucose uptake. To test this hypothesis expression of all known glucose transport proteins has been assessed at the transcript level in yellow and in silver eels, and we also included Anguillicola crassus infected swimbladders. Glucose uptake by rete mirabile endothelial cells could be crucial for the countercurrent exchange capacity of the rete. Therefore, this tissue was also included in our analysis. The results revealed expression of ten different members of the slc2 family of glucose transporters, of four slc5 family members, and of kiaa1919 in gas gland tissue. Glucose transporters of the slc2 family were expressed at very high level, and slc2a1b made up about 80% of all slc2 family members, irrespective of the developmental state or the infection status of the eel. Overall, the slc5 family contributed to only about 8% of all detected glucose transport transcripts in gas gland tissue, and the slc2 family to more than 85%. In rete capillaries, the contribution of sodium-dependent glucose transporters was significantly higher, leaving only 66% for the slc2 family of glucose transporters. Neither silvering nor the infection status had a significant effect on the expression of glucose transporters in swimbladder gas gland tissue, suggesting that glucose metabolism of eel gas gland cells may not be related to transcriptional changes of glucose transport proteins.

Although pathogens such as nematodes are known to hijack nutrients from host plants, the mechanisms whereby nematodes obtain sugars from plants remain largely unknown. To determine the effects of nematode infection on host plant sugar allocation, soluble sugar (fructose, glucose, sucrose) content was investigated using high-performance liquid chromatography with refractive index detection and was found to increase significantly in tomato ( Solanum lycopersicum , Sl ) leaves and roots during early infection by root-knot nematodes (RKNs). To further analyze whether sugar transporters played a role in this process, the expression levels of sucrose transporter ( SUT/SUC ), Sugars Will Eventually be Exported Transporter ( SWEET ), tonoplast monosaccharide transporter ( TMT ), and vacuolar glucose transporter ( VGT ) gene family members were examined by qRT-PCR analysis after RKN infection. The results showed that three SlSUTs , 17 SlSWEETs , three SlTMTs , and SlVGT1 were upregulated in the leaves, whereas three SlSUTs , 17 SlSWEETs , two SlTMTs , and SlVGT1 were induced in the roots. To determine the function of the sugar transporters in the RKN infection process, we examined post-infection responses in the Atsuc2 mutant and pAtSUC2-GUS lines. β-glucuronidase expression was strongly induced at the infection sites, and RKN development was significantly arrested in the Atsuc2 mutant. Taken together, our analyses provide useful information for understanding the sugar transporter responses during early infection by RKNs in tomato., Competing Interests: The authors have declared that no competing interests exist.

Body weight gain (BWG) and gastrointestinal nematode challenge (GIN) were investigated in two genetically diverse groups of cattle. Thirty-two dairy calves (D=Swedish Red/Holstein) and 31 dairy×beef crosses (C=Swedish Red/Holstein×Charolais) pairwise matched by dam breed and birth dates, were monitored for ≈20 weeks on a pasture grazed by cattle in the previous year. At turn-out, animals (between 6 and 12 months age) from each genotype were either infected with 5000 third stage (L3) Ostertagia ostertagi (50%) and Cooperia oncophora (50%) larvae (H, high-exposure); or treated monthly with 0.5mg ivermectin (Noromectin ® , Pour-on) per kg bodyweight to remove worms ingested (L, low-exposure). Animals were weighed every fortnight and individual BWG was calculated. Faecal and blood samples were collected every four weeks throughout the experiment for nematode faecal egg counts (FEC) and larvae cultures and serum pepsinogen concentrations (SPC), respectively. Nematode eggs were observed 29 days post turn-out in both H groups. FEC peaked to around 200 eggs per gram (epg) on days 58 and 85 respectively in both H groups. FEC were also observed in the L groups at the same time, but mean epg remained very low (<20epg) and constituted exclusively of C. oncophora. Although, there was no significant difference in SPC values in animals of the different genotypes, ten animals of CH showed a SPC >3.5 IU tyrosine whereas only six DH animals reached similar pepsinogen levels. The level of infection (H and L) significantly affected BWG in both genotypes. Even though there was no statistically significant genotype (C or D)×treatment (H or L) interaction, there was a larger difference in body weight of H and L in C (37kg) compared to D (17kg) genotypes at the end of the experiment. Our data collectively support the view crossbred (C) animals experience the impact of gastrointestinal parasitism more severely compared to pure dairy (D) first season grazers. The mechanisms that underpin this remains speculative., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Gastrointestinal nematodes (GINs), Haemonchus contortus, are a major health problem in goat production. Resistance to H. contortus, the most prevalent GIN in Uganda, was studied among three indigenous goat breeds to assess their differences. Twelve male goats of each breed approximately 7 months old of small East African (SEA), Mubende, and Kigezi goats from smallholder farmers in Arua, Mubende, and Kabale were assembled for the study. At the station, they were dewormed with a combination therapy of the broad-spectrum dewormers closantel and albendazole to free the goats of gastrointestinal parasites. During experimentation, the goats were kept indoors and ad libitum fed on clean banana peels and napier grass. On attainment of zero-worm-egg status, the goats were artificially infected with 18,000 third-stage (L3) larvae of H. contortus prepared according to Baermann's procedure. Data were collected on fecal egg count (FEC), packed cell volume (PCV), and body weight (BW) on a 2-week basis until 12 weeks post infection and carcass weight and total worm count (WC) in the abomasum at termination of the experiment. The data on FEC, PCV, and BW were subjected to repeated-measure analysis of variance and the others by one-way analysis of variance. FEC between breeds was only significantly different at 12 weeks post infection (p = 0.04). Generally, higher FEC was recorded in Kigezi compared to SEA and Mubende goats. Carcass weight was significantly different among breeds (p < 0.05), with Mubende having the highest carcass weight, followed by Kigezi and SEA. PCV and daily weight gains were significantly different between breeds (p < 0.05). WC was not significantly different between the breeds. FEC and PCV were weakly significant at later stages of the experiment with higher parasite burden suggesting potential variation in resistance to H. contortus. These differences could be exploited in designing breeding programs with disease resistance in indigenous goat breeds.

Using Illumina sequencing, we investigated transcriptional changes caused by the nematode Anguillicola crassus within yellow and silver eels by comparing swimbladder samples of uninfected yellow with infected yellow eels, and uninfected silver with infected silver eels, respectively. In yellow eel gas gland, the infection caused a modification of steady state mRNA levels of 1675 genes, most of them being upregulated. Functional annotation analysis based on GO terms was used to categorize identified genes with regard to swimbladder metabolism or response to the infection. In yellow eels, the most prominent category was 'immune response', including various inflammatory components, complement proteins, and immunoglobulins. The elevated expression of several glucose and monocarboxylate transporters indicated an attempt to maintain the level of glucose metabolism, even in due to the infection thickened swimbladder tissue. In silver eel swimbladder tissue, on the contrary, the mRNA levels of only 291 genes were affected. Genes in the categories 'glucose metabolism' and 'ROS metabolism' barely responded to the infection and even the reaction of the immune system was much less pronounced compared to infected yellow eels. However, in the category 'extracellular matrix', the mRNA levels of several mucin genes were strongly elevated, suggesting increased mucus production as a defense reaction against the parasite. The present study revealed a strong reaction to an Anguillicola crassus infection on mRNA expression levels in swimbladder tissue of yellow eels, whereas in silver eels the changes ware almost negligible. A possible explanation for this difference is that the silvering process requires so much energy that there is not much scope to cope with the additional challenge of a nematode infection. Another possible explanation could be that gas-secreting activity of the silver eel swimbladder was largely reduced, which could coincide with a reduced responsiveness to other challenges, like a nematode infection.

This study compared the phenotypic susceptibility of Pelibuey and Katahdin female lambs against gastrointestinal nematodes (GINs) under grazing conditions in the hot humid tropics of Mexico. The study was performed during the rainy season (August to October, 2014). It included 27 Pelibuey and 12 Katahdin female lambs from 6 months of age and live weight of 21.0 ± 3.7 and 23.3 ± 3.6 kg, respectively. Lambs were reared free of GIN infection before the study. The study lasted 91 days. Animals were weighed and sampled (blood and feces) on days 0 and 28 and every 7 days onwards. Fecal samples were obtained to determine fecal eggs of GIN per gram (EPG), and blood samples were used to determine the packed cell volume (PCV), the peripheral eosinophil counts (PECs), and optical densities (ODs) for IgA. The EPG counts were significantly lower for Pelibuey lambs compared to Katahdin throughout the study (P < 0.001). Similarly, Pelibuey lambs had higher mean PCV (P < 0.01) and PEC (P < 0.05) than Katahdin lambs during the study. The total weight gain and OD for IgA were similar between breeds (P > 0.05). Negative associations (P < 0.05) between EPG and PCV or PEC were moderate to strong for the lambs of both breeds. No association was found between EPG and IgA. In conclusion, Pelibuey lambs showed phenotypic evidence of higher resistance to natural GIN infections compared to Katahdin lambs sharing the same grazing conditions in the hot humid tropics. The most accurate phenotypic markers to identify a difference in susceptibility were EPG and PEC.

Parasitic worms infect billions of people worldwide. Current treatments rely on a small group of drugs that have been used for decades. A shortcoming of these drugs is their inability to target the intractable infectious stage of the parasite. As well-known therapeutic targets in mammals, nuclear receptors have begun to be studied in parasitic worms, where they are widely distributed and play key roles in governing metabolic and developmental transcriptional networks. One such nuclear receptor is DAF-12, which is required for normal nematode development, including the all-important infectious stage. Here we review the emerging literature that implicates DAF-12 and potentially other nuclear receptors as novel anthelmintic targets.

Resistance of sheep to the gastrointestinal nematode Teladorsagia circumcincta is a heritable characteristic. Control of parasite colonization and egg production is strongly linked to IgA antibody levels regulated by Th2 T cell activation within lymphoid tissue; and persistently-infected susceptible animals develop an inflammatory Th1/Th17 response within the abomasum that fails to control infection. Differential T cell polarization therefore is associated with parasite resistance and/or susceptibility and is controlled by a specific set of transcription factors and cytokine receptors. Transcript variants of these genes have been characterized in sheep, while in humans and mice different variants of the genes are associated with inflammatory diseases. RT-qPCR was used to quantify mucosal expression of the transcript variants of the sheep genes in trickle-infected animals with defined phenotypic traits. Genes that encode full-length GATA3 and IL17RB were shown to be significantly increased in resistant sheep that had controlled parasite infection. Expression levels of both were significantly negatively correlated with abomasal worm count (a parameter of susceptibility) and positively correlated with body weight (a parameter of resistance). These data show that polarized Th2 T cells within the abomasal mucosa play an important role in the maintenance of resistance., Competing Interests: This work was funded by public access research council funds (BBSRC and AHDB Beef and Lamb, both UK Government). Sheep Improved Genetics Ltd supported the application for funding but no funding was obtained from SIG Ltd. Neither the funding agencies nor SIG Ltd had a participatory role in the project, were not involved in study design or in the collection, analysis and interpretation of data or the preparation of this manuscript. None of the authors have any commercial association with the funding agencies or SIG Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This study aimed to investigate the effect of selection for low faecal egg count (FEC) in Scottish Cashmere goats in comparison to a control line of unselected goats grazing the same pasture. Goats from generations F2 through to F9 were monitored for FEC, bodyweight, peripheral eosinophilia and IgG, IgA and IgE response against Teladorsagia circumcincta from the end of their first grazing season, through winter housing (during which a single artificial challenge dose of 10,000 drug susceptible T. circumcincta was given) and the following full grazing season. The study demonstrated that selected line animals excreted a significantly lower number of parasite eggs (P<0.01) in the majority of generations examined. Liveweight productivity was unaffected by selection. Although selected line animals had greater numbers of circulating eosinophils in many of the generations (four generations of males and six generations of females, P<0.05), there was no direct link between eosinophilia and reduced FEC. Immunoglobulin levels showed no consistent difference between selected and control lines. IgG, IgA and IgE levels were not different between lines over the whole dataset (P>0.05), although the selected line had significantly elevated or reduced levels (P<0.05) for all three within individual generations. There were significant associations between increased IgG and reduced FEC under artificial infection conditions (P=0.02). Increased IgA was also significantly associated with elevated FEC during the second grazing season (P<0.001). The study demonstrates that selection produced a line of goats with consistently reduced FEC compared with control animals, but did not identify a clear relationship between any of the immune markers measured and faecal egg output., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes., (© 2016 John Wiley & Sons Ltd.)

The control of gastrointestinal nematodes (GIN) is mainly based on the use of drugs, grazing management, use of copper oxide wire particles and bioactive forages. Resistance to anthelmintic drugs in small ruminants is documented worldwide. Host genetic resistance to parasites, has been increasingly used as a complementary control strategy, along with the conventional intervention methods mentioned above. Genetic diversity in resistance to GIN has been well studied in experimental and commercial flocks in temperate climates and more developed economies. However, there are very few report outputs from the more extensive low-input/output smallholder systems in developing and emerging countries. Furthermore, results on quantitative trait loci (QTL) associated with nematode resistance from various studies have not always been consistent, mainly due to the different nematodes studied, different host breeds, ages, climates, natural infections versus artificial challenges, infection level at sampling periods, among others. The increasing use of genetic markers (Single Nucleotide Polymorphisms, SNPs) in GWAS or the use of whole genome sequence data and a plethora of analytic methods offer the potential to identify loci or regions associated nematode resistance. Genomic selection as a genome-wide level method overcomes the need to identify candidate genes. Benefits in genomic selection are now being realised in dairy cattle and sheep under commercial settings in the more advanced countries. However, despite the commercial benefits of using these tools, there are practical problems associated with incorporating the use of marker-assisted selection or genomic selection in low-input/output smallholder farming systems breeding schemes. Unlike anthelmintic resistance, there is no empirical evidence suggesting that nematodes will evolve rapidly in response to resistant hosts. The strategy of nematode control has evolved to a more practical manipulation of host-parasite equilibrium in grazing systems by implementation of various strategies, in which improvement of genetic resistance of small ruminant should be included. Therefore, selection for resistant hosts can be considered as one of the sustainable control strategy, although it will be most effective when used to complement other control strategies such as grazing management and improving efficiency of anthelmintics currently., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Soybean cyst nematode (SCN; Heterodera glycines Ichinohe) reproduces on the roots of common bean (Phaseolus vulgaris L.) and can cause reductions in plant growth and seed yield. The molecular changes in common bean roots caused by SCN infection are unknown. Identification of genetic factors associated with SCN resistance could help in development of improved bean varieties with high SCN resistance. Gene expression profiling was conducted on common bean roots infected by SCN HG type 0 using next generation RNA sequencing technology. Two pinto bean genotypes, PI533561 and GTS-900, resistant and susceptible to SCN infection, respectively, were used as RNA sources eight days post inoculation. Total reads generated ranged between ~ 3.2 and 5.7 million per library and were mapped to the common bean reference genome. Approximately 70-90% of filtered RNA-seq reads uniquely mapped to the reference genome. In the inoculated roots of resistant genotype PI533561, a total of 353 genes were differentially expressed with 154 up-regulated genes and 199 down-regulated genes when compared to the transcriptome of non- inoculated roots. On the other hand, 990 genes were differentially expressed in SCN-inoculated roots of susceptible genotype GTS-900 with 406 up-regulated and 584 down-regulated genes when compared to non-inoculated roots. Genes encoding nucleotide-binding site leucine-rich repeat resistance (NLR) proteins, WRKY transcription factors, pathogenesis-related (PR) proteins and heat shock proteins involved in diverse biological processes were differentially expressed in both resistant and susceptible genotypes. Overall, suppression of the photosystem was observed in both the responses. Furthermore, RNA-seq results were validated through quantitative real time PCR. This is the first report describing genes/transcripts involved in SCN-common bean interaction and the results will have important implications for further characterization of SCN resistance genes in common bean.

Genetic markers for sheep resistance to gastrointestinal parasites have long been sought by the livestock industry as a way to select more resistant individuals and to help farmers reduce parasite transmission by identifying and removing high egg shedders from the flock. Polymorphisms related to the major histocompatibility complex and interferon (IFN)-γ genes have been the most frequently reported markers associated with infection. Recently, a new picture is emerging from genome-wide studies, showing that not only immune mechanisms are important determinants of host resistance but that gastrointestinal mucus production and hemostasis pathways may also play a role., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Research has shown that Toll-like receptor 4 (TLR4) is important in immune responses to some helminth parasites. In sheep, variation in the PAMP region of TLR4 may result in structurally and thus functionally different TLR4 molecules, and this may consequently lead to variation in the TLR4 response to parasite infections. This study involved three separate, but related sheep breeds (Merino, Polwarth and Corriedale sheep) and a total of 885 lambs from five New Zealand farms that underwent a mixed field-challenge from gastro-intestinal parasites. Faecal samples were collected at approximately 4 and 9 months of age and faecal egg counts (FECs) for Nematodirus spp. and Strongyle species determined, along with the total number of eggs per gram (EPG). Analysis of the five farms collectively revealed an association (P=0.023) between the presence of TLR4 variant *02 (mean 24 EPG) and the absence of the variant (mean 32 EPG) at 9 months of age. Conversely the presence of *03 had a significantly (P=0.047) higher mean Nematodirus spp. FEC (mean 42 EPG) compared to the absence (mean 28 EPG) at 9 months of age. More associations were revealed when the data were split according to the dominant faecal parasite species. With a predominantly Trichostrongylus spp. FEC group of lambs at 9 months of age, the presence of TLR4 variant *02 was found to have significantly (P=0.003) lower Nematodirus spp. FEC (mean 4 EPG), and also significantly (P=0.033) lower total FEC (mean 312 EPG) when compared to sheep without the variant (mean 15 EPG and 449 EPG, respectively). The presence of TLR4 variant *03 and *04 were associated or tended to be associated (P=0.010 and P=0.088, respectively) with higher Nematodirus spp. FEC (mean 25 EPG and 22 EPG, respectively) when compared to lambs without the variant (mean 10 EPG and 11 EPG, respectively). These results suggest that TLR4 variation may be affecting the immune response to gastro-intestinal parasites in sheep, although principally to Nematodirus spp. infections and not Strongyle species infections., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Intestinal nematode infection and dietary protein deficiency are common during pregnancy and both have been shown to impair fetal growth in humans, livestock and laboratory animals. The placenta has been linked to fetal growth but its role in mediating the response to maternal infection and protein deficiency is not understood. We used microarrays to test the hypothesis that maternal intestinal nematode infection and protein deficiency alter the expression of placental genes related to fetal growth. Placentas were obtained on day 18 of pregnancy from CD-1 mice fed protein sufficient (24%) or protein deficiency (6%) isoenergetic diets and either uninfected or infected with Heligmosomoides bakeri. Gene expression was analysed using the Affymetrix GeneChip 2.0 ST mouse array (n=3/experimental group). Differentially expressed genes were identified using two-way ANOVA (P<0.02, fold-change >1.25) and pathway analyses were performed using DAVID software. Expression changes for selected genes were confirmed using qPCR. Heligmosomoides bakeri infection down-regulated 109 transcripts, including genes related to oxidative phosphorylation, and up-regulated 214 transcripts, including genes involved in ATP binding and hemopoiesis. Up-regulation of hemopoiesis genes may explain increased placental mass previously reported in H. bakeri-infected mice. Protein deficiency down-regulated 141 annotated transcripts, including genes involved in cell motility and endopeptidase activity, and up-regulated 131 annotated transcripts, including genes related to hemopoiesis. A statistical interaction was detected for 248 transcripts, including several genes with known functions in fetal growth. Notably, expression of the gene Irs1 (insulin receptor substrate) was lower in infected dams but only when they were fed a protein sufficient diet. Also, expression of several genes, including Igf1r (insulin-like growth factor-1 receptor) and Prl (prolactin) was up-regulated by infection in protein deficiency dams and down-regulated by protein deficiency in uninfected dams. Our results highlight that expression of placental genes involved in fetal growth is influenced by the interaction between protein deficiency and H. bakeri infection., (Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Chitinase-like proteins (CLPs) of the 18 glycosyl hydrolase family retain structural similarity to chitinases but lack enzymatic activity. Although CLPs are upregulated in several human disorders that affect regenerative and inflammatory processes, very little is known about their normal physiological function. We show that an insect CLP (Drosophila imaginal disc growth factor 3, IDGF3) plays an immune-protective role during entomopathogenic nematode (EPN) infections. During these infections, nematodes force their entry into the host via border tissues, thus creating wounds. Whole-genome transcriptional analysis of nematode-infected wild-type and Idgf3 mutant larvae have shown that, in addition to the regulation of genes related to immunity and wound closure, IDGF3 represses Jak/STAT and Wingless signaling. Further experiments have confirmed that IDGF3 has multiple roles in innate immunity. It serves as an essential component required for the formation of hemolymph clots that seal wounds, and Idgf3 mutants display an extended developmental delay during wound healing. Altogether, our findings indicate that vertebrate and invertebrate CLP proteins function in analogous settings and have a broad impact on inflammatory reactions and infections. This opens the way to further genetic analysis of Drosophila IDGF3 and will help to elucidate the exact molecular context of CLP function., (© 2015 The Author(s) Published by S. Karger AG, Basel.)

This paper considers genetic resistance to infectious disease in sheep, with appropriate comparison with goats, and explores how such variation may be used to assist in disease control. Many studies have attempted to quantify the extent to which host animals differ genetically in their resistance to infection or in the disease side-effects of infection, using either recorded animal pedigrees or information from genetic markers to quantify the genetic variation. Across all livestock species, whenever studies are sufficiently well powered, then genetic variation in disease resistance is usually seen and such evidence is presented here for three infections or diseases of importance to sheep, namely mastitis, foot rot and scrapie. A further class of diseases of importance in most small ruminant production systems, gastrointestinal nematode infections, is outside the scope of this review. Existence of genetic variation implies the opportunity, at least in principle, to select animals for increased resistance, with such selection ideally used as part of an integrated control strategy. For each of the diseases under consideration, evidence for genetic variation is presented, the role of selection as an aid to disease control is outlined and possible side effects of selection in terms of effects in performance, effects on resistance to other diseases and potential parasite/pathogen coevolution risks are considered. In all cases, the conclusion is drawn that selection should work and it should be beneficial, with the main challenge being to define cost effective selection protocols that are attractive to sheep farmers., (Copyright © 2015. Published by Elsevier B.V.)