Novel gene expression responses in the ovine abomasal mucosa to infection with the gastric nematode Teladorsagia circumcincta

Pamela A Knight,Ivan W Morrison,Stewart Tg Burgess,Alan L Archibald,David W Smith,Alan D Pemberton,Lauren Guarneri,Mark Fell,Richard T Talbot,Katherine Anderson,David Waddington,Judith M Pate,Sarah Smith,Hugh Rp Miller,Susan E Griffith

doi:10.1186/1297-9716-42-78

Pamela A Knight, Ivan W Morrison + Show 13 more

Open Access

https://doi.org/10.1186/1297-9716-42-78

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Abstract

Infection of sheep with the gastric nematode Teladorsagia circumcincta results in distinct Th2-type changes in the mucosa, including mucous neck cell and mast cell hyperplasia, eosinophilia, recruitment of IgA/IgE producing cells and neutrophils, altered T-cell subsets and mucosal hypertrophy. To address the protective mechanisms generated in animals on previous exposure to this parasite, gene expression profiling was carried out using samples of abomasal mucosa collected pre- and post- challenge from animals of differing immune status, using an experimental model of T. circumcincta infection. Recently developed ovine cDNA arrays were used to compare the abomasal responses of sheep immunised by trickle infection with worm-naïve sheep, following a single oral challenge of 50 000 T. circumcincta L3. Key changes were validated using qRT-PCR techniques. Immune animals demonstrated highly significant increases in levels of transcripts normally associated with cytotoxicity such as granulysin and granzymes A, B and H, as well as mucous-cell derived transcripts, predominantly calcium-activated chloride channel 1 (CLCA1). Challenge infection also induced up-regulation of transcripts potentially involved in initiating or modulating the immune response, such as heat shock proteins, complement factors and the chemokine CCL2. In contrast, there was marked infection-associated down-regulation of gene expression of members of the gastric lysozyme family. The changes in gene expression levels described here may reflect roles in direct anti-parasitic effects, immuno-modulation or tissue repair. (Funding; DEFRA/SHEFC (VT0102) and the BBSRC (BB/E01867X/1)).

Highlights

Parasitic gastroenteritis (PGE), caused by trichostrongylid nematodes, is the most commonly diagnosed systemic disease of sheep in the U.K
To identify the molecular changes generated in the abomasal mucosa in animals after previous exposure to this parasite, gene expression profiling was carried out using ovine cDNA microarrays on samples of abomasal mucosa collected pre- and post-challenge from animals of differing immune status
Our data presented here are consistent with the observed increased adaptive and innate immune response taking place by days 2 and 5 postchallenge in the abomasal mucosa of sheep previously exposed to the parasite using this experimental protocol [11]

Summary

Introduction

Parasitic gastroenteritis (PGE), caused by trichostrongylid nematodes, is the most commonly diagnosed systemic disease of sheep in the U.K. Immunity builds up slowly on repeated exposure to the parasite, indicating vaccination could be a feasible alternative, but vaccine development is hampered by a lack of knowledge of the host-parasite interaction to infective accompanied by distinct Th2-type changes in the mucosa, such as mucous neck cell and mast cell hyperplasia, eosinophilia, recruitment of IgA/IgE producing cells and neutrophils, altered T-cell subsets and mucosal hypertrophy [10,11,12,13,14]. The molecular changes involved, and the relative contributions of these factors to both control of infection and the clinical symptoms of disease, are still poorly understood. To identify the molecular changes generated in the abomasal mucosa in animals after previous exposure to this parasite, gene expression profiling was carried out using ovine cDNA microarrays on samples of abomasal mucosa collected pre- and post-challenge from animals of differing immune status.

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