Abstract

This study exploited Blackface lambs that varied in their resistance to the abomasal nematode parasite, Teladorsagia circumcincta. Infection of these lambs over 3 months identified susceptible (high adult worm count, high faecal egg count and low IgA antibody) and resistant animals that had excluded all parasites. Previous work had shown that susceptibility and resistance is dependent on the differential immune response to the parasite, which occurs within the abomasal (gastric) lymph node (ALN) that drains the site of infection. The Affymetrix ovine gene array was used to interrogate the transcriptome of the ALN to identify genes and physiological pathways associated with resistance. We used a bovine RT-qPCR array of 84 genes to validate the gene array, and also report digital gene expression analysis on the same tissues, reanalysed using the Oar v3.1 sheep genome assembly. These analyses identified Humoral Immune Response, Protein Synthesis, Inflammatory Response and Hematological System Development and Function as the two top-ranked networks associated with resistance. Central genes within these networks were IL4, IL5, IL13RA2 and in particular IL13, which confirmed that differential activation of Th2 polarized responses is critical to the resistance phenotype. Furthermore, in resistant sheep there was up-regulation of genes linked to control and suppression of inflammation. The identity of differentially-expressed chemokines and receptors in the resistant and susceptible sheep also begins to explain the cellular nature of the host response to infection. This work will greatly help in the identification of candidate genes as potential selectable markers of genetic resistance.

Highlights

  • Gastrointestinal nematode parasites are the cause of major economic losses to the sheep agricultural industry [1] and the major species in cool temperate regions is the abomasal strongylid Teladorsagia circumcincta [1,2]

  • One strategy for the non-pharmacological control of parasites is the exploitation of genetic variation for resistance found within and between different sheep breeds [20,21]

  • This regime resulted in lambs with a range of resistance as assessed by adult worm counts, faecal egg counts (FEC) and IgA levels. Previous studies with these sheep used digital gene expression (DGE) [24] and RT-qPCR [33] to conclude that both resistance and susceptibility are active responses to infection; and that the inflammatory lesions of the susceptible sheep are associated with differential activation of Th17 T cells. The aim of this project was to investigate genes and physiological pathways associated with the differential activation of the immune response linked to the different disease outcomes

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Summary

Introduction

Gastrointestinal nematode parasites are the cause of major economic losses to the sheep agricultural industry [1] and the major species in cool temperate regions is the abomasal strongylid Teladorsagia circumcincta [1,2]. The control of this parasite is largely by the use of broad-spectrum anthelmintics [3,4] but the increasing incidence of drug-resistant parasites and concern of drug residues in meat [5] has led to the search for alternative methods of parasite management [6]. One strategy for the non-pharmacological control of parasites is the exploitation of genetic variation for resistance found within and between different sheep breeds [20,21]

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