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Immunological insights into equine responses against Strongylus vulgaris : Ex vivo studies using equine intestinal organoids and blood mononuclear cells

Hellman, Stina (2021). Immunological insights into equine responses against Strongylus vulgaris : Ex vivo studies using equine intestinal organoids and blood mononuclear cells. Diss. (sammanfattning/summary) Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880
ISBN 978-91-7760-825-7
eISBN 978-91-7760-826-4
[Doctoral thesis]

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Abstract

Anthelminthic drugs have controlled parasitic infections in veterinary species for decades, but today this use is questioned due to concerns about antimicrobial resistance. For most microorganisms, a feasible alternative is vaccination but for parasites, commercial vaccines are scarce. This is partly due to the complex life cycles of most helminths together with their immunomodulatory capacity. In the horse, Strongylus vulgaris has recently gained attention due to its re-emergence in Sweden. The overall aim of the present thesis was therefore to establish ex vivo methods to study responses against S. vulgaris that can guide formulation of a future vaccine. In the search for relevant antigens, protocols for generating defined larval (L) stages were established. These S. vulgaris preparations, alone or in combination with an adjuvant, were evaluated for their cytokine-inducing capacity. All larval preparations induced a Th2 profile in equine PBMC characterised by up-regulation of IL-4, IL-5, IL-9, IL-13 and TSLP. The L4 stage skewed this response by also up-regulating IFN-γ. The presence of a novel saponin adjuvant affected the Th2 profile induced by the L3 stage of S. vulgaris. To study responses to S. vulgaris at the site of infection, equine intestinal stem cells were differentiated into intestinal organoids. From these, monolayer cultures were established that displayed both genetic and functional similarities with the equine intestine, expressing pro-inflammatory cytokine genes at exposure to TLR-agonists. These organoid monolayers were applicable for generation of ex vivo co-cultures with equine PBMC and S. vulgaris larvae. Overall, this thesis provides new insights into the biology of S. vulgaris infection and ex vivo methods that will aid in the development of a future vaccine.

Authors/Creators:Hellman, Stina
Title:Immunological insights into equine responses against Strongylus vulgaris : Ex vivo studies using equine intestinal organoids and blood mononuclear cells
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :2021
Number:2021:74
Number of Pages:105
Publisher:Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-825-7
ISBN for electronic version:978-91-7760-826-4
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Article category:Other scientific
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Keywords:Strongylus vulgaris, enteroids, equine, PBMC, ex vivo, parasite
URN:NBN:urn:nbn:se:slu:epsilon-p-113848
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-113848
ID Code:25569
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:07 Oct 2021 08:25
Metadata Last Modified:07 Oct 2021 08:31

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