Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands.
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ABSTRACT:
SUBMITTER: Guo Z
PROVIDER: S-EPMC4873755 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands.
Guo Zhengyu Z González Jorge Francisco JF Hernandez Julia N JN McNeilly Tom N TN Corripio-Miyar Yolanda Y Frew David D Morrison Tyler T Yu Peng P Li Robert W RW
Scientific reports 20160520
Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resis ...[more]
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Project description:BackgroundThe integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying the resistance of hosts to parasites. Haemonchus contortus, the predominant sheep gastrointestinal parasite species in the tropics, causes significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control owing to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control.MethodsEggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with H. contortus and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50 K single-nucleotide genotyping. Additionally, RNA-seq data for H. contortus were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content.ResultsThe heritability estimate for EPG was 0.12. GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. Trans-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to H. contortus, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera; Prevotellaceae family; and Verrucomicrobiota phylum. In H. contortus, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep.ConclusionsThe present study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota, and the H. contortus parasite. These findings will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus infection in sheep.
| S-EPMC10908167 | biostudies-literature
Project description:Our objective was to investigate differences in gene expression between 24 parasite-resistant hair and 24 susceptible wool lambs to determine genetic mechanisms involved in resistance to H. contortus. Half of the animals of each breed were infected and sacrificed at 3 or 27 days post-infection; the remaining animals were uninfected controls. Breed differences in abomasum and abomasal lymph node tissue gene expression were assessed using bovine cDNA microarrays. Over 60 transcripts differed between breeds for each tissue and infection status. Genes differentially expressed between hair and wool sheep 3 days PI were assessed for gene function and mechanisms for greater immune cell infiltration, abomasal tissue repair, Th17 response, and anticoagulation were present in parasite-resistant hair sheep. By 27 days PI, hair sheep had greater expression of genes involved in gut motility, inflammatory cytokines, and cell proliferation and differentiation compared to wool sheep. Changes in these processes indicate Caribbean hair sheep have a stronger inflammatory response when infected with H. contortus which may facilitate the increased parasite resistance observed in these sheep.
2009-03-31 | GSE14667 | GEO
Project description:Haemonchus contortus is a highly pathogenic parasitic nematode of that can infect a large number of wild and domesticated ruminant species and is the most economically important parasite of sheep and goats worldwide. Although originally a tropical parasite, it has been disseminated around the world by livestock movement and can now be found as far north as the arctic circle. Adult worms are blood feeders that reside in the abomasum (stomach) and are approximately 2cm in length when mature. They are dioecious with single females typically producing several thousand eggs per day which pass out of the host in faeces and develop to infective larvae on the pasture. H. contortus is a member of the superfamily trichostrongyloidea (Strongylida) which contains most of the economically important parasitic nematodes of grazing livestock. These parasites cost the global livestock industry billions of dollars per annum in lost production and drug costs. Resistance to all the major anthelmintic classes is now common worldwide often leading to failure of treatment and control. H. contortus is a close relative of the human hookworm species and belongs to the nearest phylogenetic group of parasites to the free-living model nematode Caenorhabditis elegans . This makes it an important model of parasitic nematode biology that is commonly used for experimental studies. The main objective of this project is to recognize genes expressed in the life stages of H. contortus.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2013-02-12 | E-ERAD-143 | biostudies-arrayexpress
Project description:Culture-independent methods were used to study the microbiota of adult worms, third-stage larvae and eggs, both in faeces and laid in vitro, of Haemonchus contortus, a nematode parasite of the abomasa of ruminants which is a major cause of production losses and ill-health. Bacteria were identified in eggs, the female reproductive tract and the gut of adult and third-stage larvae (L3). PCR amplification of 16S rRNA sequences, denaturing gradient gel electrophoresis (DGGE) and clone libraries were used to compare the composition of the microbial communities of the different life-cycle stages of the parasites, as well as parasites and their natural environments. The microbiomes of adult worms and L3 were different from those in the abomasum or faeces respectively. The H. contortus microbiota was mainly comprised of members of the phyla Proteobacteria, Firmicutes and Bacteroidetes. Bacteria were localised in the gut, inside eggs and within the uterus of adult female worms using the universal FISH Eub338 probe, which targets most bacteria, and were also seen in these tissues by light and transmission electron microscopy. Streptococcus/Lactococcus sp. were identified within the distal uterus with the probe Strc493. Sequences from the genera Weissella and Leuconostoc were found in all life-cycle stages, except eggs collected from faeces, in which most sequences belonged to Clostridium sp. Bacteria affiliated with Weissella/Leuconostoc were identified in both PCR-DGGE short sequences and clone libraries of nearly full length 16S rRNA bacterial sequences in all life-cycle stages and subsequently visualised in eggs by fluorescent in situ hybridisation (FISH) with group-specific probes. This strongly suggests they are vertically transmitted endosymbionts. As this study was carried out on a parasite strain which has been maintained in the laboratory, other field isolates will need to be examined to establish whether these bacteria are more widely dispersed and have potential as targets to control H. contortus infections.
| S-EPMC5805237 | biostudies-literature
Project description:This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 associated with resistance to the abomasal nematode Haemonchus contortus. The first objective was to validate the identified QTL through the comparison of genetically susceptible (N) and resistant (R) sheep produced from Martinik?×?Romane back-cross sheep. The R and N genotype groups were then experimentally infected with 10 000?H. contortus larvae and measured for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences in FEC and haematocrit drop were found between R and N sheep. In addition, the female worms recovered from R sheep were less fecund. The second step of the characterization was to investigate functional mechanisms associated with the QTL, thanks to a gene expression analysis performed on the abomasal mucosa and the abomasal lymph node. The gene expression level of a candidate gene lying within the QTL region (PAPP-A2) was measured. In addition, putative interactions between the chromosome segment under study and the top ten differentially expressed genes between resistant MBB and susceptible RMN sheep highlighted in a previous microarray experiment were investigated. We found an induction of Th-2 related cytokine genes expression in the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression was observed between naïve and challenged sheep although no differential expression was recorded between challenged R and N sheep. The genotyping of this limited region should contribute to the ability to predict the intrinsic resistance level of sheep.
| S-EPMC4077151 | biostudies-literature
Project description:BACKGROUND:Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode, Haemonchus contortus. Host genetic variation for resistance to H. contortus allows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimate Fst outliers in three different breeds of sheep and goats exposed to H. contortus. RESULTS:Our results for sheep populations showed SNPs under selection in C3AR1, CSF3, SOCS2, NOS2, STAT5B, TGFB2 and IL2RA genes using frequentist and Bayesian approaches. For goats, SNPs in CD1D, ITGA9, IL12A, IL13RA1, CD86 and TGFB2 genes were under selection. Common signatures of selection in both species were observed in NOS2, TGFB2 and TLR4 genes. Directional selection was present in all SNPs evaluated in the present study. CONCLUSIONS:A total of 13 SNPs within 7 genes of our candidate gene panel related to H. contortus exposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance to H. contortus is likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection against H. contortus infection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.
| S-EPMC6792194 | biostudies-literature
Project description:Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.
| S-EPMC7695930 | biostudies-literature
Project description:Haemonchus contortus is one of the most pathogenic gastrointestinal nematodes in small ruminants. To understand molecular mechanisms underlying host resistance to this parasite, we used RNA-sequencing technology to compare the transcriptomic response of the abomasal tissue, the site of the host-parasite interaction, of Merino sheep bred to be either genetically resistant or susceptible to H. contortus infection. Two different selection flocks, the Haemonchus selection flock (HSF) and the Trichostrongylus selection flock (TSF), and each contains a resistant and susceptible line, were studied. The TSF flock was seemingly more responsive to both primary and repeated infections than HSF. A total of 127 and 726 genes displayed a significant difference in abundance between resistant and susceptible animals in response to a primary infection in HSF and TSF, respectively. Among them, 38 genes were significantly affected by infection in both flocks. Gene ontology (GO) enrichment of the differentially expressed genes identified in this study predicted the likely involvement of extracellular exosomes in the immune response to H. contortus infection. While the resistant lines in HSF and TSF relied on different mechanisms for the development of host resistance, adhesion and diapedesis of both agranulocytes and granulocytes, coagulation and complement cascades, and multiple pathways related to tissue repair likely played critical roles in the process. Our results offered a quantitative snapshot of changes in the host transcriptome induced by H. contortus infection and provided novel insights into molecular mechanisms of host resistance.
| S-EPMC6345051 | biostudies-literature
Project description:Once Haemonchus contortus infects sheep it receives a series of host attacks, especially those relating to the infected animal’s T lymphocytes immune response. To obtain a systematic genome-wide profiling of the T lymphocyte genes involved, microarrays were used to compare gene expression between 0 days post infection (dpi), 3-5 dpi, 25-30 dpi and 60dpi in infected sheep. In this 853, 242 and 42 differentially expressed genes were acquired in the 3d vs. 0d comparison, the 30d vs. 0d comparison and the 60d vs. 0d comparison, respectively. Gene Ontology and pathway analysis indicated that modulated genes including SUGT1, FCER1G, CD23, IL-13 and galectin-14, were mostly associated with cellular homeostasis maintaining and immune response.
2012-11-16 | GSE42302 | GEO
Project description:The immune response against Haemonchus contortus infections is primarily associated with the Th2 profile. However, the exact mechanisms associated with increased sheep resistance against this parasite remains poorly elucidated. The present study is aimed at evaluating mediators from the innate immune response in lambs of the Morada Nova Brazilian breed with contrasting H. contortus resistance phenotypes. Briefly, 287 lambs were characterized through fecal egg counts (FEC) and packed cell volume (PCV) after two independent experimental parasitic challenges with 4,000 H. contortus L3. 20 extreme resistance phenotypes (10 most resistant and 10 most susceptible) were selected, subjected to a third artificial infection with 4,000 L3, and euthanized 7 days later. Tissue samples were collected from abomasal fundic and pyloric mucosa and abomasal lymph nodes. Blood samples were collected at days 0 and 7 of the third parasitic challenge. RNA was extracted from tissue and blood samples for relative quantification of innate immune-related genes by RT-qPCR. For the abomasal fundic mucosa, increased TNF? and IL1? expression levels (P < 0.05) were found in the susceptible animals, while resistant animals had IL33 superiorly expressed (P < 0.05). Higher levels (P < 0.05) of TLR2 and CFI were found in the abomasal pyloric mucosa of resistant animals. TNF? was at higher levels (P < 0.05) in the blood of susceptible lambs, at day 0 of the third artificial infection. The exacerbated proinflammatory response observed in susceptible animals, at both local and systemic levels, may be a consequence of high H. contortus parasitism. This hypothesis is corroborated by the higher blood levels of TNF? before the onset of infection, which probably remained elevated from the previous parasitic challenges. On the other hand, resistant lambs had an enhanced response mediated by TLR recognition and complement activation. Nevertheless, this is the first study to directly associate sheep parasitic resistance with IL33, an innate trigger of the Th2-polarized response.
| S-EPMC6877983 | biostudies-literature