Abstract
This study used selected lambs that varied in their resistance to the gastrointestinal parasite Teladorsagia circumcincta. Infection over 12 weeks identified susceptible (high adult worm count, AWC; high fecal egg count, FEC; low body weight, BW; low IgA) and resistant sheep (no/low AWC and FEC, high BW and high IgA). Resistance is mediated largely by a Th2 response and IgA and IgE antibodies, and is a heritable characteristic. The polarization of T cells and the development of appropriate immune responses is controlled by the master regulators, T-bet (TBX21), GATA-3 (GATA3), RORγt (RORC2) and RORα (RORA); and several inflammatory diseases of humans and mice are associated with allelic or transcript variants of these transcription factors. This study tested the hypothesis that resistance of sheep to T. circumcincta is associated with variations in the structure, sequence or expression levels of individual master regulator transcripts. We have identified and sequenced one variant of sheep TBX21, two variants of GATA3 and RORC2 and five variants of RORA from lymph node mRNA. Relative RT-qPCR analysis showed that TBX21, GATA3 and RORC2 were not significantly differentially-expressed between the nine most resistant (AWC, 0; FEC, 0) and the nine most susceptible sheep (AWC, mean 6078; FEC, mean 350). Absolute RT-qPCR on all 45 animals identified RORVv5 as being significantly differentially-expressed (p = 0.038) between resistant, intermediate and susceptible groups; RORCv2 was not differentially-expressed (p = 0.77). Spearman’s rank analysis showed that RORAv5 transcript copy number was significantly negatively correlated with parameters of susceptibility, AWC and FEC; and was positively correlated with BW. RORCv2 was not correlated with AWC, FEC or BW but was significantly negatively correlated with IgA antibody levels. This study identifies the full length RORA variant (RORAv5) as important in controlling the protective immune response to T. circumcincta infection in sheep.
Highlights
The abomasal strongylid Teladorsagia circumcincta is a major cause of sheep parasitic gastroenteritis [1, 2]
The induction of the immune response to these parasites occurs in the draining abomasal lymph node (ALN) and the events within that node are likely to determine the quality and quantity of the response that occurs within the mucosa and the consequent clinical outcome
RORC2 is encoded on the minus strand of chromosome 1 (NC_019468) and, in comparison to the full length gene (LN848233), RORC2v1 (LN848234) has a 36 bp deletion (g.1237_1272del) at the 3’ end of exon 7 (Chr1: 100,653,158–100,653,123), which represents the deletion of 12 amino acids (GKYGGVELFRAL) at position 359–370 (S3 Fig) of RORγt
Summary
The abomasal strongylid Teladorsagia circumcincta is a major cause of sheep parasitic gastroenteritis [1, 2]. The most susceptible animals are weaned lambs [3], but many eventually suppress larval development and egg production [4] through the development of IgA and IgE antiparasite antibodies [5,6,7]. IgA levels and fecal egg counts (FEC) have been used as selectable markers for resistance [4, 8, 9] and antigens that promote the production of abomasal IgA antibodies have been identified as potential vaccine candidates [10]. Several studies have analysed abomasal mucosa to identify genes associated with resistance to T. circumcincta or the related parasite Haemonchus contortus [12,13,14]. The induction of the immune response to these parasites occurs in the draining abomasal (gastric) lymph node (ALN) and the events within that node are likely to determine the quality and quantity of the response that occurs within the mucosa and the consequent clinical outcome
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