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Further work on host parasite interactions, including the potential for the control of sheep scab using immunological approaches, and the development of diagnostic tools - OD0555

Description
Current research at Moredun has used transcriptome analysis and quantitative gene expression studies (by microarray) to investigate the host response to sheep scab mite, Psoroptes ovis. We are analysing the interaction between host gene response to infestation and the mites’ own gene response from the start of infection, through to the resolving stage of the lesion. Analysis of sheep skin lesion biopsies over a 6 week infection with P. ovis revealed the significant differential expression of >1000 host genes during the first 24 hours of infection. Many of these genes are involved in the immune response and include cytokines, chemokines, anti-microbial and pro-inflammatory factors. A pathway mapping approach has allowed us to identify the key host signaling pathways critical for the establishment of the mite. The use of specific pathway inhibitors both in vitro (in our ovine keratinocyte culture system) and in vivo will allow the specific blockade of selected pathways to determine their importance in the development of the sheep scab lesion. This process, combined with data from the P. ovis cDNA microarray, will allow us to identify mite factors that instigate and maintain the lesion.
The mite factors which are involved in the triggering of these host signaling pathways are being determined through the use of a P. ovis cDNA microarray, which provides a unique resource for investigating those factors critical for the establishment and maintenance of the lesion. During the initial part of this process we have already identified a potent pro-inflammatory mite factor. Further analyses will reveal further factors, and these are prime vaccine candidates. Moreover, these ‘lesion-inducing’ proteins are likely to represent critical factors in mite virulence which have been shown to be an important variable in natural sheep scab outbreaks.
Previous studies at Moredun have also identified breed specific differences in the host response to P. ovis infection. Analysis of our host skin response data has identified the differential expression of a number of genes from the epidermal differentiation complex (EDC) which is critical for the maintenance of an effective skin barrier. Altered expression of EDC genes, or polymorphisms in them, are both implicated in the pathogenesis of allergic diseases. We propose to test for the presence of polymorphisms within EDC genes in two breeds of sheep; Blackface and Dorset, which have known differences in susceptibility to P. ovis infection.
In addition to the above studies, a highly sensitive diagnostic assay based on the detection of antibody has been developed. All the analyses so far have shown that this assay is sensitive and specific, and is based on the reactivity to a recombinant protein. A lateral flow ‘dipstick’ test is being developed, but requires further development and validation in the field.
Further development of a control method for sheep scab, based on our current understanding of the disease and the interactions between parasite and host, will therefore follow a defined course, based on the above. It is envisaged that vaccine development or alternative control strategies will be developed, and that an assay to rapidly and reliably detect sheep scab will be developed for use in the field.
Time-Scale and Cost
From: 2010

To: 2013

Cost: £825,805
Contractor / Funded Organisations
Moredun Research Institute
Keywords
Animal Diseases              
Animal Health              
Endemic              
Parasites              
Plants and Animals              
Sheep              
Sheep Scab              
Fields of Study
Animal Health