Abstract
BackgroundSheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response.ResultsThrough a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators.ConclusionsInterrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.
Highlights
Sheep scab, caused by the mite Psoroptes ovis is highly contagious, causing pruritis and irritation
The life cycle of P. ovis is completed entirely upon the host [4] and mites survive on the surface of the skin, though their mouthparts do not appear to penetrate beyond the stratum corneum [5]
P. ovis mites were applied to the skin of sheep (n = 6) and skin biopsy samples were removed following 1, 3, 6 and 24 hours of exposure along with reference biopsies
Summary
Sheep scab, caused by the mite Psoroptes ovis is highly contagious, causing pruritis and irritation It is a major welfare concern in livestock production in many areas of the world [1] and is currently the most important ectoparasitic disease of sheep in the UK. The available evidence suggests that mites abrade the stratum corneum, depositing allergens as they progress This combination of skin abrasion, allergen deposition and selfgrooming behaviour, initiated by the host in response to the pruritis caused by the mites, triggers the subsequent activation of a cutaneous inflammatory response [6] including an exudate which supplies the mite with a food source consisting of serous fluids, lymph and blood cells [7,8]. Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response
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