Galectin secretion and binding to adult Fasciola hepatica during chronic liver fluke infection of sheep
- Authors: Young, Anna , Barcham, Garry , McWilliam, Hamish , Piedrafita, David , Meeusen, Els
- Date: 2012
- Type: Text , Journal article
- Relation: Veterinary Immunology and Immunopathology Vol. 145, no. 1-2 (2012), p. 362-367
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- Description: Galectins are increasingly recognised as important mediators of immune homeostasis and disease regulation, but comparatively little is known about their role in parasite infection. This study investigates the interaction between two ovine galectins, galectin-11 and galectin-14, and the parasitic liver fluke, F. hepatica. Galectin-14 was found in eosinophils infiltrating the tissue surrounding infected bile ducts and secreted in the connective tissue, while galectin-11 was specifically induced in epithelial cells of bile ducts from infected sheep. Strong nuclear staining was observed for galectin-11. Both galectins were found to be secreted into the bile fluid of parasite infected sheep, and were also detected in the excretory/secretory products of adult flukes, following their removal from the ovine host. Recombinant galectin-14, but not recombinant galectin-11, was found to bind specifically to the surface tegument of adult flukes in a carbohydrate dependent manner. This study shows for the first time that both galectin-14 and galectin-11 are produced in liver tissue after chronic liver fluke infection and that they can directly interact with the parasite in the bile ducts. Galectin-11 may also be involved in epithelial cell turnover and cancerogenesis.
The kinetics of local cytokine and galectin expression after challenge infection with the gastrointestinal nematode, Haemonchus contortus
- Authors: Robinson, Nicholas , Pleasance, Jill , Piedrafita, David , Meeusen, Els
- Date: 2011
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 41, no. 5 (2011 2011), p. 487-493
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- Description: Gastrointestinal nematode parasites undergo several developmental stages within their mammalian host, each presenting different antigenic challenges to the immune system. To examine the expression of different immune mediators over time, biopsy samples were collected from the cannulated abomasum (true stomach) of immune sheep at several times after a challenge infection with Haemonchus contortus L3s. IL-5 and IL-13 mRNA expression levels were significantly increased above saline-challenged control levels at 5 and 7 days post challenge, while IL-4 showed an earlier peak at day 2 post challenge. IL-5, IL-13 and IL-4, as well as IFN-
The relationship between the rapid rejection of Haemonchus contortus larvae with cells and mediators in abomasal tissues in immune sheep
- 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.
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
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- 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
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- 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.