Ovine Disease Resistance: Integrating comparative and functional genomics approaches in a genome information-poor Species
- Authors: Raadsma, Herman , Fullard, K.J. , Kingsford, Nicola , Margawati, Endang , Estuningsih, Endah , Widajayanti, S. , Subandriyo, N. , Clairoux, N. , Spithill, Terry , Piedrafita, David
- Date: 2008
- Type: Text , Book chapter
- Relation: Genomics of Disease Chapter 3 p. 89-113
- Full Text: false
- Reviewed:
Low cost whole-organism screening of compounds for anthelmintic activity
- Authors: Preston, Sarah , Jabbar, Abdul , Nowell, Cameron , Joachim, Anja , Ruttkowski, Barbel , Baell, Jonathan , Cardno, Tony , Korhonen, Pasi , Piedrafita, David , Ansell, Brendan , Jex, Aaron , Hofmann, Andreas , Gasser, Robin
- Date: 2015
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 45, no. 5 (2015), p. 333-343
- Full Text: false
- Reviewed:
- Description: Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. contortus by measuring the inhibition of larval motility using an automated image analysis system. We identified two chemicals within the compound classes biphenyl amides and pyrazolo[1,5-α]pyridines, which reproducibly inhibit both xL3 and L4 motility and development, with IC50s of 14-47μM. Given that these inhibitors were designed as anti-inflammatory drugs for use in humans and fit the Lipinski rule-of-five (including bioavailability), they show promise for hit-to-lead optimisation and repurposing for use against parasitic nematodes. The screening assay established here has significant advantages over conventional methods, particularly in terms of ease of use, throughput, time and cost. Although not yet fully automated, the current assay is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation. The current assay is highly adaptable to many parasites of socioeconomic importance, including those causing neglected tropical diseases. This aspect is of major relevance, given the urgent need to deliver the goals of the London Declaration (
Modulation of Haemonchus contortus infection by depletion of γδ+ T cells in parasite resistant Canaria Hair Breed sheep
- Authors: Hernández, Julia , Meeusen, Els , Stear, Michael , Rodríguez, Francisco , Piedrafita, David , Gonzalez, Jorge
- Date: 2017
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 237, no. (2017), p. 57-62
- Full Text: false
- Description: Canaria Hair Breed (CHB) sheep display resistance against the adult stage of the nematode, Haemonchus contortus. Previous studies have suggested significant correlations between γδ+ T lymphocytes and fecundity of female adult worms, suggesting a novel role in immune modulation by these cells. The largest proportion of γδ+ T lymphocytes in sheep are the subpopulation of γδ+/WC1+ T cells. The aim of this study was to evaluate the effect of γδ+/WC1+ T cell depletion via infusion of anti-γδ/WC1 monoclonal antibody (mAb) on the subsequent immune response of CHB sheep infected with H. contortus. Significantly lower γδ+ T cell levels in both peripheral blood and in the basal layers of the abomasal tissue resulted following anti-γδ/WC1 mAb infusion of CHB sheep compared to control animals. Worms recovered from the anti-γδ/WC1 mAb treated CHB sheep had significantly longer female worms with correspondingly more eggs in utero than the saline control group. Significant correlations between eosinophils and worm length and fecundity were no longer apparent in the anti-γδ/WC1 mAb treated CHB sheep. These results support the notion that γδ+ T cells in CHB sheep play a critical role in fecundity regulation (length and eggs in utero) of H. contortus adult female worms, and highlights a new mechanism of modulation by this lymphocyte population, possibly involving eosinophil activation. © 2017 Elsevier B.V.
Cloning, expression, purification and crystallographic studies of galectin-11 from domestic sheep (Ovis aries)
- Authors: Sakthivel, Dhanasekaran , Littler, Dene , Shahine, Adam , Troy, Sally , Johnson, Matthew , Rossjohn, Jamie , Piedrafita, David , Beddoe, Travis
- Date: 2015
- Type: Text , Journal article
- Relation: Acta Crystallographica Section:F Structural Biology Communications Vol. 71, no. (2015), p. 993-997
- Full Text:
- Reviewed:
- Description: Galectins are an evolutionarily conserved family of proteins that translate glycan recognition into cellular effects. Galectin-11 is a unique member of the galectin family that is only expressed in ruminants such as sheep, goat and cattle and that plays a critical role in several important biological processes, such as reproduction and parasite-mediated innate immune responses. Currently, these two areas are of major importance for the sustainability of ruminant livestock production. Despite the emerging biological significance of galectin-11, no structural information is available. It is expected that structural studies will unravel the functional mechanisms of galectin-11 activity. Here, the expression, purification and crystallization of the ruminant-specific galectin-11 from domestic sheep and the collection of X-ray data to 2.0 Å resolution are reported. © 2015.
Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus
- Authors: Sakthivel, Dhanasekaran , Swan, Jaclyn , Preston, Sarah , Shakif-Azam, MD , Faou, Pierre , Jiao, Yaqing , Downs, Rachael , Rajapaksha, Harinda , Gasser, Robin , Piedrafita, David , Beddoe, Travis
- Date: 2018
- Type: Text , Journal article
- Relation: Peerj Vol. 6, no. 3 (2018), p. 1-19
- Full Text:
- Reviewed:
- Description: Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins) when compared to the larval stage (two proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS- 14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.
Potential role for mucosal IgA in modulating Haemonchus contortus adult worm infection in sheep
- Authors: Hernández, Julia , Hernández, Alvaro , Stear, Michael , Conde-Felipe, Magnolia , Rodríguez, Eduardo , Piedrafita, David , Gonzalez, Jorge
- Date: 2016
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 223, no. (2016), p. 153-158
- Full Text: false
- Reviewed:
- Description: Haemonchus contortus (H. contortus) is a haematophagous parasite which causes important economic losses in small ruminants. On the island of Gran Canaria, two sheep breeds coexist which differ in their susceptibility to the infection with H. contortus; the resistant Canaria Hair Breed (CHB) sheep and the susceptible Canaria Sheep (CS) breed. The major target of resistance mechanisms in CHB sheep are directed to the adult parasite stage, reducing the worm burden, and decreased length and fecundity of surviving worms. Mucosal IgA (mIgA) has been shown to be an important regulator of immunity in Haemonchus and Teladorsagia infections; through correlations with larval stages where such mechanisms as antibody-dependent cell cytotoxicity and enzyme inhibition may mediate resistance. Here for the first time, we demonstrate a significant negative correlation between mIgA and adult worm length and fecundity only in the resistant CHB sheep. In contrast, and as reported in other sheep breeds, mIgA was only negatively correlated against the larval stage in the more susceptible CS breed. This study suggests mIgA may play a role in resistance to both larval and adult stages. © 2016 Elsevier B.V.
The composition and stability of the faecal microbiota of merino sheep
- Authors: Mamun, Mohammed , Sandeman, Mark , Rayment, Philip , Brook-Carter, Phillip , Scholes, Emily , Kasinadhuni, Naga , Piedrafita, David , Greenhill, Andrew
- Date: 2020
- Type: Text , Journal article
- Relation: Journal of Applied Microbiology Vol. 128, no. 1 (2020), p. 280-291
- Full Text: false
- Reviewed:
- Description: Aims: To determine the composition and temporal stability of the gut (faecal) microbiota of sheep (Ovis aries). Methods and Results: Microbial population dynamics was conducted using ARISA (28 sheep) and 16S rRNA sequencing (11 sheep). Firmicutes and Bacteroidetes were the predominant bacterial phyla, constituting ~80% of the total population. The core faecal bacterial microbiota of sheep consisted of 67 of 136 detected families and 91 of 215 detected species. Predominant microbial taxa included Ruminococcaceae, unassigned families in Bacteroidales and Clostridiales, Verrucomicrobiaceae and Paraprevotellaceae. Diversity indices and core microbiota composition demonstrated the stability of the core microbiota over 2–4 weeks. The core microbiota remained similar over ~5 months. Conclusions: Temporal stability of the sheep microbiota is high over 2–4 weeks in the absence of experimental variables. The core microbiota of Merino sheep shares taxa found in other breeds of sheep and other ruminants. Significance and Impact of the Study: Numerous studies seek to investigate the impact of experimental variables on gut microbiota composition. To do so, knowledge of the innate stability (or instability) of the microbiota over an experimental time course is required, independent of other variables. We have demonstrated high stability of the gut microbiota in sheep over 3–4 weeks, with moderate stability over ~5 months. © 2019 The Society for Applied Microbiology
Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
- Authors: Rajapaksa, Anushi , Ho, Jenny , Qi, Aaisha , Bischof, Robert , Nguyen, Tri-Hung , Tate, Michelle , Piedrafita, David , McIntosh, Michelle , Yeo, Leslie , Meeusen, Els , Coppel, Ross , Friend, James
- Date: 2014
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 15, no. 1 (2014), p. 1-12
- Full Text:
- Reviewed:
- Description: Background: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization.Methods: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep.Results: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.Conclusion: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways. © 2014 Rajapaksa et al.; licensee BioMed Central Ltd.
Development and application of a faecal antigen diagnostic sandwich ELISA for estimating prevalence of Fasciola gigantica in cattle in central Java, Indonesia
- Authors: Estuningsih, Endah , Spithill, Terry , Raadsma, Herman , Law, Ruby , Adiwinata, G. , Meeusen, Els , Piedrafita, David
- Date: 2009
- Type: Text , Journal article
- Relation: Journal of Parasitology Vol. 95, no. 2 (2009), p. 450-455
- Full Text: false
- Reviewed:
- Description: The purpose of this study was to compare the sensitivity and specificity of an ELISA test to detect Fasciola gigantica antigens (coproantigens) in bovine feces, with fecal egg counting and an ELISA for detecting anti-F. gigantica antibodies in serum. Monoclonal antibodies to cathepsin L were generated and used to capture this antigen in feces of infected cattle. Blood, feces, and livers were collected from 150 cattle at an abattoir in Jakarta, Indonesia, for anti-Fasciola antibodies, coproantigen detection, and F. gigantica egg and worm counts. Fluke recovery varied from 1 to 426 per host, with a mean of 32 flukes. The results showed that the sensitivity and specificity of coproantigen detecting ELISA (95 and 91%, respectively) was better than the anti-F. gigantica antibody ELISA (91 and 88%, respectively) and to fecal egg counting (87 and 100%, respectively). The coproantigen ELISA was able to detect 100% of the cattle with >15 flukes. A survey of 305 cattle in central Java over a 10-mo period validated this test in the field, demonstrating a high prevalence of fascioliasis and establishing the test as a useful diagnostic method to determine patent F. gigantica infections in cattle.
The current status of anthelmintic resistance in a temperate region of Australia; implications for small ruminant farm management
- Authors: Preston, Sarah , Piedrafita, David , Sandeman, Mark , Cotton, Steve
- Date: 2019
- Type: Text , Journal article
- Relation: Veterinary Parasitology: Regional Studies and Reports Vol. 17, no. (2019), p.
- Full Text: false
- Reviewed:
- Description: Widespread anthelmintic resistance in small ruminants is a constraint on the profitability of the meat/wool industry. Limited published data is available on the prevalence and efficacy of anthelmintics, particularly in Australia where parasites affecting ruminant systems vary greatly between geographic regions. This paper reports on the anthelmintic resistance status in a temperate region of Victoria, Australia, a major sheep producing state largely affected by Trichostrongylus species and Teladorsagia circumcincta. The prevalence of anthelmintic resistance to any product was high (71%), with farms reporting varying levels of drug efficacies (21–100%). Resistance to older chemical groups (i.e. fenbendazole and levamisole) and single active macrocyclic lactone treatments was higher than newer chemical groups and combination treatments. This report provides clarity on anthelmintic resistance in the temperate region of Victoria and more importantly suggests that more comprehensive, regional specific anthelmintic resistance studies are required to understand the real level of chemical resistance threatening the effective control of worms. © 2019
Selection of multi-drug resistant influenza A and B viruses under zanamivir pressure and their replication fitness in ferrets
- Authors: Oh, Ding , Panozzo, Jacqueline , Vitesnik, Sophie , Piedrafita, David , Mosse, Jennifer
- Date: 2018
- Type: Text , Journal article
- Relation: Antiviral Therapy Vol. 23, no. 4 (2018), p. 295-306
- Full Text: false
- Reviewed:
- Description: Background: Intravenous zanamivir has been used to treat patients with severe influenza. Because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. Therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important. Methods: Influenza A(H1N1)pdm09, A(H3N2) and B virus were serially passaged under increasing zanamivir pressure in vitro. Neuraminidase (NA) mutations that arose were introduced into recombinant viruses and the susceptibility to oseltamivir, zanamivir, peramivir and laninamivir was determined. The replication fitness of the recombinant variants was assessed in the ferret. Results: NA mutations E119D (N1 numbering) and E117D (B numbering) were detected in A(H1N1)pdm09 and B (Victoria-lineage) viruses respectively and were associated with reduced susceptibility to all four NA inhibitors. No NA mutations were detected in the A(H3N2) or B (Yamagata-lineage) viruses. In ferrets, the A(H1N1) pdm09 E119D variant caused a lower degree of morbidity and the mutation was found to be unstable with E119 reverted virus detected 4 days post-infection of ferrets with the variant E119D virus. In contrast, the influenza B E117D variant was genetically stable in ferrets, caused a noticeable level of morbidity but had a significant reduction in replication fitness compared to wild-type virus. Conclusions: The NA mutations E119D in influenza A(H1N1)pdm09 and E117D in influenza B viruses that arose under zanamivir pressure conferred resistance to multiple NA inhibitors but had compromised viral replication in ferrets compared to wild-type virus without antiviral drug pressure. ©2018 International Medical Press. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Jacqueline Panozzo, David Piedrafita, Jennifer Mosse” is provided in this record**
The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
- Authors: Sakthivel, Dhanasekaran , Preston, Sarah , Gasser, Robin , Meeusen, Els , Piedrafita, David
- Date: 2020
- Type: Text , Journal article
- Relation: Communications Biology Vol. 3, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Dhanasekaran Sakthivel, Sarah Preston, Robin Gasser, Els Meeusen, David Piedrafita” is provided in this record**
Comparative evaluation of different molecular methods for DNA extraction from individual Teladorsagia circumcincta nematodes
- Authors: Sloan, Shelly , Jenvey, C. J. , Piedrafita, David , Preston, Sarah , Stear, Michael
- Date: 2021
- Type: Text , Journal article
- Relation: Bmc Biotechnology Vol. 21, no. 1 (May 17 2021), p.
- Full Text:
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Quantifying the sources of variation in eosinophilia among Scottish blackface lambs with mixed, predominantly Teladorsagia circumcincta nematode infection
- Authors: Jenvey, Caitlin , Almasi, Fazel , Halliwell, Emma , Piedrafita, David , Preston, Sarah
- Date: 2021
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 300, no. (2021), p.
- Full Text:
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- Description: Eosinophils play a key role in defence against gastrointestinal nematodes. There is considerable variation among animals in the intensity of eosinophilia following nematode infection. However, the statistical distribution of eosinophils among animals has still to be determined. A better description of the variation among animals could provide biological insight and determine the most appropriate way to analyse the effect of eosinophils. We estimated blood eosinophil numbers in a flock of Scottish Blackface sheep that were naturally exposed to mixed, predominantly Teladorsagia circumcincta infection. Three of the four eosinophil counts were better described by a gamma distribution than by a lognormal distribution. The scale and shape parameters of the gamma distribution varied over time. Eosinophil counts differed among animals kept on separate fields before weaning and between singletons and twins but were not significantly different between years and genders. Eosinophil counts also differed among offspring from different sires and dams. The parameters of the gamma distribution were used to enable a power analysis. Large numbers of animals were required to reliably detect even large differences between two groups. These results indicate that methods appropriate for gamma distributions, such as generalized linear mixed models, will provide more reliable inferences than traditional methods of analysis and experimental design. © 2021 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “David Piedrafita and Sarah Preston” is provided in this record**
Increased susceptibility to Haemonchus contortus infection by interleukin-5 modulation of eosinophil responses in sheep
- Authors: Hernández, Julia , Meeusen, Els , Rodríguez, Francisco , Piedrafita, David , González, Jorge
- Date: 2020
- Type: Text , Journal article
- Relation: Parasite Immunology Vol. 42, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Eosinophils are prominent effector cells in immune responses against gastrointestinal nematode infections in ruminants, but their in vivo role has been hard to establish in large animals. Interleukin-5 is a key cytokine in the induction and stimulation of anti-parasitic eosinophil responses. This study attempted to modulate the eosinophil response in sheep through vaccination with recombinant interleukin-5 (rIL-5) and determine the effect on subsequent Haemonchus contortus infection. Nematode-resistant Canaria Hair Breed (CHB) sheep vaccinated with rIL-5 in Quil-A adjuvant, had lower blood eosinophil counts and higher mean worm burdens than control sheep vaccinated with Quil-A adjuvant alone. In addition, adult worms in IL-5-vaccinated sheep were significantly longer with higher eggs in utero in female worms, supporting an active role of eosinophils against adult parasites in CHB sheep. These results confirm that eosinophils can play a direct role in effective control of H contortus infection in sheep and offer a new approach to study immune responses in ruminants. © 2019 John Wiley & Sons Ltd
Vaccines for fasciola : new thinking for an old problem
- Authors: Spithill, Terry , Toet, Hayley , Rathinasamy, Vignesh , Zerna, Gemma , Swan, Jaclyn , Cameron, Timothy , Smooker, Peter , Piedrafita, David , Dempster, Robert , Beddoe, Travis
- Date: 2021
- Type: Text , Book chapter
- Relation: Fasciolosis II Chapter 12 p. 379-422
- Full Text: false
- Reviewed:
Investigation of the combined efficacy of two Haemonchus contortus vaccines in weaner Merino sheep
- Authors: Kebeta, M. M. , Hine, Brad , Walkden-Brown, Stephen , Kahn, Lewis , Piedrafita, David , Bailey, S. , Doyle, Emma
- Date: 2022
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 301, no. (2022), p.
- Full Text: false
- Reviewed:
- Description: This study was conducted to investigate whether co-administration of Barbervax® (Bvax) with Haemonchus contortus surface larval antigen (HcsL3) would increase the protective efficacy and duration of protection against H. contortus infection in weaner Merino sheep. A total of 132 10-month-old weaned Merino ewe lambs were randomly allocated into six treatment groups (n = 22). Sheep were vaccinated four times with either Barbervax® (Bvax), H. contortus L3 surface larval antigen (HcsL3), combined vaccination (Bvax + HcsL3), Bvax + AlOH, HcsL3 + Saponin or remained as unvaccinated controls. Aluminium hydroxide (AlOH) and saponin adjuvants were included in HcsL3 and Bvax vaccines respectively. The first three vaccinations were given at 4 week intervals and the fourth vaccination provided as booster, 9 weeks later. All animals were treated with Zolvix™ (monepantel 25 mg/mL, Elanco) at the third vaccination and commencing two weeks later, artificially trickle infected with H. contortus L3. Worm egg count (WEC), packed cell volume (PCV), antibody titre and bodyweight were measured throughout the study as was specific antibody directed against each antigen using ELISA. The administration of Bvax and HcsL3, alone or in combination, induced an antibody response against HcsL3 but only the Bvax and the combined treatment elicited an antibody response to the Bvax antigen. The targeting of HcsL3 by each vaccine was confirmed by immunofluorescence staining of H. contortus L3. However, only the booster vaccination in the Bvax treatments reduced WEC to levels below untreated controls. The HcsL3 vaccine did not reduce WEC in this experiment and co-administration with Bvax did not improve the efficacy and duration of protection against H. contortus infection. © 2021 Elsevier B.V.
The heritability of Nematodirus battus fecal egg counts
- Authors: Nikbin, Saeid , Almasi, Fazel , Alenizi, Dalal , Jenvey, Caitlin , Sloan, Sarah , Preston, Sarah , Piedrafita, David , Jonsson, Nicholas , Stear, Michael
- Date: 2022
- Type: Text , Journal article
- Relation: Parasitology Vol. 149, no. 4 (2022), p. 555-561
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- Reviewed:
- Description: Although Nematodirus battus is a serious threat to the health and survival of young lambs, there are few options to control this parasite. Bayesian Monte Carlo Markov Chain modelling with a zero-inflated Poisson distribution was used to estimate the heritability of egg counts in both June and July for each of five consecutive cohorts of 200 Scottish Blackface lambs. In one of the 10 analyses, the results failed the diagnostic tests. In seven of the analyses, there was no convincing evidence that the variation in egg counts was heritable. In the 2 years of high infection, the heritability was approximately 0.4 in June but the estimates lacked precision and the 95% highest posterior density credible intervals ranged from just above zero to 0.7. Selective breeding for resistance to N. battus will be difficult because genetically resistant or susceptible lambs cannot be consistently identified by phenotypic markers. © The Author(s) 2022.
Evaluation of the role of galectins in parasite immunity
- Authors: Swan, Jaclyn , Sakthivel, Dhanasekaran , Beddoe, Travis , Stear, Michael , Piedrafita, David , Preston, Sarah
- Date: 2022
- Type: Text , Book chapter
- Relation: Galectins: Methods in Molecular Biology Chapter 7 p. 475-515
- Full Text: false
- Reviewed:
- Description: Galectin-11 (LGALS-11) and galectin-14 (LGALS-14) are ruminant specific galectins, first reported in sheep. Although their roles in parasite immunity are still being elucidated, it appears that they influence protection against parasites. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. To unravel the structural, functional, and ligand profile of galectin-11 and galectin-14, recombinant production of these proteins is vital. Here we present the recombinant production of soluble galectin-11 and galectin-14 from domestic sheep for in vitro and structural biology studies. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins, pull-down assays to identify endogenous galectin binding proteins, and in vitro assays to monitor the effect of galectins on parasite development. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.
The immune response to nematode infection
- Authors: Stear, Michael , Preston, Sarah , Piedrafita, David , Donskow-Łysoniewska, Katarzyna
- Date: 2023
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 24, no. 3 (2023), p.
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- Description: Nematode infection is a major threat to the health of humans, domestic animals and wildlife. Nematodes vary in their effect on the host and in the mechanisms underlying immunity but the general features are becoming clear. There is considerable variation among individuals in resistance to infection and much of this variation is due to genetic variation in the immune response. The major histocompatibility complex has a strong influence on resistance to infection but other genes are collectively more important. Resistant individuals produce more IgA, eosinophils, IgE and mast cells than susceptible individuals and this is a consequence of stronger type 2 (Th2) immune responses. A variety of factors promote Th2 responses including genetic background, diet, molecules produced by the parasite and the location of the infection. A variety of cells and molecules including proteins, glycolipids and RNA act in concert to promote responses and to regulate the response. Nematodes themselves also modulate the host response and over 20 parasite-derived immunomodulatory molecules have been identified. Different species of nematodes modulate the immune response in different ways and probably use multiple molecules. The reasons for this are unclear and the interactions among immunomodulators have still to be investigated. © 2023 by the authors.