GSE63547
Transcriptional profiling of the ovine abomasal lymph node reveals a role for timing of the immune response in gastrointestinal nematode resistance
Background: Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, which develops over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable (h ~ 0.3). A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid future breeding strategies as well as 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 lambs. Results: Scottish Blackface lambs, with divergent phenotypes for resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3), and abomasal lymph node recovered at 7 and 14 days post-infection (dpi). High-throughput sequencing of abomasal lymph node cDNA 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. Resistant animals appear to generate a more rapid immune response as at 7 dpi processes relating to homing of lymphocytes, leukocyte migration and migration of antigen presenting cells were up-regulated. In susceptible animals this response appears to be delayed until approximately 14 dpi. Twenty-four Single Nucleotide Polymorphims (SNP), within 11 differentially expressed genes were tested for association with gastrointestinal nematode resistance in the Scottish Blackface lambs. Four SNPs in two genes (SLC30A2, and ALB) were suggestively associated with faecal egg count. Conclusions: 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 a more rapid immune response to T. circumcincta. In susceptible lambs this response appears to be delayed until approximately 14 days post infection. SNP in two differentially expressed genes were suggestively associated with faecal egg count indicating that differentially expressed genes can be considered as candidate loci for mediating nematode resistance. Overall design: Scottish Blackface lambs, selected for divergent phenotypes for nematode resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3) and abomasal lymph node recovered at 7 and 14 days post-infection for transcriptome sequencing.