Transcriptional profiling of the ovine abomasal lymph node reveals a role for timing of the immune response in gastrointestinal nematode resistance.

Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, with protective immunity developing over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable. A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid both future breeding strategies and the development of effective and sustainable nematode control methods. The aim of this study was to compare the abomasal lymph node transcriptome of resistant and susceptible lambs in order to determine biological processes differentially expressed between resistant and susceptible individuals. Scottish Blackface lambs, with divergent phenotypes for resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3), and abomasal lymph nodes recovered at 7 and 14days post-infection (dpi). High-throughput sequencing of cDNA from the abomasal lymph node was used to quantitatively sample the transcriptome with an average of 32 million reads per sample. A total of 194 and 144 genes were differentially expressed between resistant and susceptible lambs at 7 and 14 dpi respectively. Differentially expressed networks and biological processes were identified using Ingenuity Pathway Analysis. Genes involved in the inflammatory response, attraction of T lymphocytes and binding of leukocytes were more highly expressed in resistant animals at 7 dpi and in susceptible animals at 14 dpi indicating that resistant animals respond to infection earlier than susceptible animals. Twenty-four Single Nucleotide Polymorphisms (SNP) within 11 differentially expressed genes, were tested for association with gastrointestinal nematode resistance in the Scottish Blackface lambs. Four SNP, in 2 genes (SLC30A2 and ALB), were suggestively associated with faecal egg count. In conclusion, a large number of genes were differentially expressed in the abomasal lymph node of resistant and susceptible lambs responding to gastrointestinal nematode challenge. Resistant Scottish Blackface lambs appear to generate an earlier immune response to T. circumcincta. In susceptible lambs this response appears to be delayed. SNP in 2 differentially expressed genes were suggestively associated with faecal egg count indicating that differentially expressed genes may be considered candidate loci for mediating nematode resistance.