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The relationship between the rapid rejection of Haemonchus contortus larvae with cells and mediators in abomasal tissues in immune sheep

- Kemp, Joanna, Robinson, Nicholas, Meeusen, Els, Piedrafita, David

  • Authors: Kemp, Joanna , Robinson, Nicholas , Meeusen, Els , Piedrafita, David
  • Date: 2009
  • Type: Text , Journal article
  • Relation: International Journal for Parasitology Vol. 39, no. 14 (2009), p. 1589-1594
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  • Description: Rapid rejection or immune exclusion of challenge larvae is a well recognised phenomenon in sheep hypersensitised by repeated infection with gastrointestinal nematodes. While mast cells and globule leukocytes (GLs) are typically associated with this rapid rejection response, the exact mechanisms and mediators involved are not known. This study has adapted a recently developed ex vivo tissue explant model to examine in more detail the cells and mediators involved in preventing establishment of Haemonchus contortus L3s in abomasal tissue of sensitised sheep. Hypersensitisation of sheep by repeated larval infection resulted in a significant inhibition of larval establishment in abomasal tissue cultures and the extent of inhibition was dependent on the sensitisation dose. Both mast cells and GLs, but not eosinophils, were increased in abomasal tissues of hypersensitised sheep. Globule leucocyte numbers decreased significantly after 3 h of culture, independent of the addition of L3s. In contrast, mast cell numbers only decreased after addition of L3s to the tissue cultures and this was associated with an increased release of histamine in tissue washes after incubation with L3s. Although, there was no significant difference in the number of tissue eosinophils between the groups, there was a marked increase in the eosinophil-specific protein, galectin-14, in tissue washes of the hypersensitised sheep after culture, suggesting eosinophils and their products may play a hitherto unrecognised role in the rapid rejection response. Further studies using specific inhibitors in this ex vivo tissue explant model may delineate the relative role of each cell population and mediator in the rapid rejection process.

Immune cell kinetics in the ovine abomasal mucosa following hyperimmunization and challenge with Haemonchus contortus

- Robinson, Nicholas, Piedrafita, David, Snibson, Kenneth, Harrison, Paul, Meeusen, Els

  • Authors: Robinson, Nicholas , Piedrafita, David , Snibson, Kenneth , Harrison, Paul , Meeusen, Els
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Veterinary Research Vol. 41, no. (2010), p. 1-7
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  • Description: Sheep were sensitized by repeated infection with Haemonchus contortus L3, followed by a 12 week rest period, and an abomasal cannula was surgically implanted in all sheep. Seven of the sensitized sheep were subsequently challenged with 50 000 H. contortus L3 while 4 control sheep were challenged with saline. Biopsy samples were taken using a fibreoptic endoscope on days 0, 1, 2, 3, 5, 7 and 28 after challenge and leukocyte subpopulations quantified by (immuno)histology. Differential blood cell counts were performed on the same days. At the end of the trial, sheep showed significantly reduced worm burdens compared to unsensitized control sheep, confirming their resistance status. Both blood and tissue eosinophils, as well as tissue

Current status for gastrointestinal nematode diagnosis in small ruminants: where are we and where are we going?

- Preston, Sarah, Sandeman, Mark, Gonzalez, Jorge, Piedrafita, David

  • Authors: Preston, Sarah , Sandeman, Mark , Gonzalez, Jorge , Piedrafita, David
  • Date: 2014
  • Type: Text , Journal article
  • Relation: Journal of immunology research Vol. 2014, no. September (2014), p. Article no. 210350
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  • Description: Gastrointestinal nematode (GIN) parasites pose a significant economic burden particularly in small ruminant production systems. Anthelmintic resistance is a serious concern to the effective control of GIN parasites and has fuelled the focus to design and promote sustainable control of practices of parasite control. Many facets of sustainable GIN parasite control programs rely on the ability to diagnose infection both qualitatively and quantitatively. Diagnostics are required to determine anthelmintic efficacies, for targeted treatment programs and selection of animals for parasite resistant breeding. This review describes much of the research investigated to date to improve the current diagnostic for the above practices which is based on counting the number of parasite eggs in faeces.

Selenophene and thiophene-core estrogen receptor ligands that inhibit motility and development of parasitic stages of Haemonchus contortus

- Preston, Sarah, Luo, Junjie, Zhang, Yuezhou, Jabbar, Abdul, Crawford, Simon, Baell, Jonathan, Hofmann, Andreas, Hu, Min, Zhou, Hai-Bing, Gasser, Robin

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

- Preston, Sarah, Korhonen, Pasi, Mouchiroud, Laurent, Cornaglia, Matteo, McGee, Sean, Young, Neil, Davis, Rohan, Crawford, Simon, Nowell, Cameron, Ansell, Brendan, Fisher, Gillian, Andrews, Katherine, Chang, Bill, Gijs, Martin, Sternberg, Paul, Auwerx, Johan, Baell, Jonathan, Hofmann, Andreas, Jabbar, Abdul, Gasser, Robin

  • Authors: Preston, Sarah , Korhonen, Pasi , Mouchiroud, Laurent , Cornaglia, Matteo , McGee, Sean , Young, Neil , Davis, Rohan , Crawford, Simon , Nowell, Cameron , Ansell, Brendan , Fisher, Gillian , Andrews, Katherine , Chang, Bill , Gijs, Martin , Sternberg, Paul , Auwerx, Johan , Baell, Jonathan , Hofmann, Andreas , Jabbar, Abdul , Gasser, Robin
  • Date: 2017
  • Type: Text , Journal article
  • Relation: FASEB Journal Vol. 31, no. 10 (2017), p. 4515-4532
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  • Description: As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation. © FASEB.

Quantifying the sources of variation in eosinophilia among Scottish blackface lambs with mixed, predominantly Teladorsagia circumcincta nematode infection

- Jenvey, Caitlin, Almasi, Fazel, Halliwell, Emma, Piedrafita, David, Preston, Sarah

  • 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.
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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**
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