Parasitology (MRI and R(D)SVS)

This component of the VTRI consortium focuses on gastrointestinal nematode infections of sheep. There are several PhD or MSc projects currently underway listed in the table below, but there is plenty of scope for more.

Two of the existing projects are applying genomic or proteomic techniques to Haemonchus contortus, whereas four are concentrating on different aspects of the core topic which is investigating the local responses to Teladorsagia (Ostertagia) circumcinta infection in the sheep. Here we are applying contemporary immunological, functional genomic and proteomic techniques to understand more about how sheep become immune to this important nematode. It is hoped that in the longer term this knowledge can be harnessed to manipulate the response in favour of the sheep ie towards immunological control through vaccination.

Sheep do acquire immunity to Teladorsagia after prior exposure to the parasite. We have a well established experimental system which demonstrates that previously infected sheep reject most of a challenge infection which establishes in naïve animals. Furthermore, a high proportion of the parasites which do manage to establish in these immune animals arrest their development at the early fourth stage and those which do continue to develop are stunted. Surprisingly perhaps, the effector mechanisms responsible for each of these different manifestations of immunity are currently unknown. We hope that this project will throw light on these phenomena.

We are monitoring the local responses of immune and naïve sheep by studying changes in the abomasal mucosa and by monitoring the flow and composition of gastric lymph which can be obtained in a physiological manner for several weeks from the same animal (Figure 1). The protein content of gastric lymph reflects that of the interstitial fluid of the abomasal mucosa and so day to day changes in the synthesis of mucosal proteins can be followed in lymph. In addition gastric lymph contains large numbers of lymphocytes (Figure 1). We are monitoring the daily traffic of these cells together with changes in their surface phenotype and their cytokine content.

Figure 1. Lymph analysis

A cDNA library has been prepared from the gastric mucosa, its draining nodes and lymph cells collected at strategic points after infection. Once this library has been sequenced microarrays will be prepared and interrogated with DNA extracted from the same tissues to discover which transcripts are up- or down-regulated during infection. It is anticipated that this will throw up several novel proteins which are associated with the pathology and / or immunity to this disease. Intelectin is an example of a novel protein identified from earlier work with rodent model gastrointestinal infections. It is up-regulated in some sheep infected with Teladorsagia but its function is not yet understood (Figure 2).

Figure 2. Expression of a novel, TH2-regulated, gene in the parasitized gastric mucosa