Transcriptional profiling of Ovis aries identifies Ovar-DQA1 allele frequency differences between nematode-resistant and susceptible selection lines.
ABSTRACT Gastrointestinal nematodes are a major cause of disease in grazing livestock; however, individual animals differ in their response to infection. To identify genes whose expression correlates with resistance status, transcriptional profiling of resistant and susceptible sheep was undertaken. Transcription profiles were taken at three time points during the growth of lambs. The number of genes differentially expressed increased as animals were exposed to longer nematode challenge. Almost 300 genes, with a variety of functions, were differentially expressed overall, although genes more highly expressed in resistant animals typically had major histocompatibility complex (MHC) II, free radical scavenging or smooth muscle-specific functions. The Ovar-DQA1 gene was 8.4-fold more highly expressed in resistant animals. This was due in part to a higher frequency of DQA1 null alleles in susceptible animals. The null allele of DQA1 was also associated with susceptibility in a separate selection flock, presenting the hypothesis that failure to present parasite antigens to immune cells led to nematode susceptibility. To test this hypothesis, commercial rams from three breeds were genotyped for the null allele of DQA1. The homozygous null allele was associated with susceptibility in only one of the three breeds tested indicating that the null allele does not cause susceptibility to intestinal parasites per se but is probably in linkage disequilibrium with additional polymorphisms in the MHC region. A combination of these polymorphisms may contribute to susceptibility in some populations. The extent of linkage disequilibrium between polymorphisms may vary from breed to breed or population to population.
Article: A differential interplay between the expression of Th1/Th2/Treg related cytokine genes in Teladorsagia circumcincta infected DRB1*1101 carrier lambs.[show abstract] [hide abstract]
ABSTRACT: ABSTRACT: Substantial debate exists on whether the immune response between sheep resistant and susceptible to gastrointestinal nematodes can be differentiated into a Th1 and Th2 phenotype. The present study addresses the hypothesis that variation in resistance to Teladorsagia circumcincta between DRB1*1101 (associated with reduced faecal egg count and worm burden) carriers and non-carriers is due to a differential interplay in the expression of Th1/Th2 and regulatory T (Treg) related cytokine genes. Lambs from each genotype were either slaughtered at day 0 (un-infected control) or infected with 3 × 104 Teladorsagia circumcincta L3 and slaughtered at 3, 7, 21, and 35 days later. Lambs carrying the DRB1*1101 allele had a significantly lower worm burden (P < 0.05) compared to the non-carriers. Abomasal mucosal cytokine gene expression was evaluated by quantitative real-time PCR and comparison made for time and genotype effects. The response generated varied through the course of infection and was affected by genotype. DRB1*1101 carriers had an up-regulated expression of the Th1-related cytokine genes (IL-1β, TNFα, and IFN-γ) at day 3, but this was replaced by an up-regulated expression of Th2-related cytokine genes (IL-10 and IL-13) and Treg-related cytokine genes (IL-2RA-CD25, TGFα, TGFβ, Arg2, MIF and FOXP3) by day 7. Conversely, in the non-carriers these changes in gene expression were delayed until days 7 and 21 post infection (pi), respectively. It is concluded that resistance to Teladorsagia circumcincta in animals carrying the DRB1*1101 allele is influenced by an earlier interplay between Th1, Th2 and T regulatory immune response genes.Veterinary Research 03/2011; 42(1):45. · 4.06 Impact Factor
Article: The influence of MHC and immunoglobulins a and e on host resistance to gastrointestinal nematodes in sheep.[show abstract] [hide abstract]
ABSTRACT: Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals.Journal of Parasitology Research 01/2011; 2011:101848.