Abstract
BackgroundInfestation of ovine skin with the ectoparasitic mite Psoroptes ovis results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the in vivo skin response to infestation with P. ovis to gain a clearer understanding of the mechanisms and signalling pathways involved.ResultsInfestation with P. ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (IL1A, IL1B, IL6, IL8 and TNF) and factors involved in immune cell activation and recruitment (SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 and CXCL2). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.ConclusionsThis study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to P. ovis, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to P. ovis, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.
Highlights
Infestation of ovine skin with the ectoparasitic mite Psoroptes ovis results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab
An intact epithelial barrier is crucial for maintenance of skin defence, preventing penetration of allergens beyond the stratum corneum and from making contact with antigen presenting cells (APCs) in subepithelial tissues [125]
P. ovis produces homologues of the house dust mite (HDM) proteolytic enzymes Der p 1 and Der p 3 which may be involved in the initial interactions with host skin via proteolytic disruption of the epidermal barrier
Summary
Infestation of ovine skin with the ectoparasitic mite Psoroptes ovis results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Mites survive on the surface of the skin and their mouthparts do not appear to penetrate beyond the stratum corneum [6]. The available evidence suggests that mites abrade the stratum corneum, depositing allergens as they progress and this combination of skin abrasion, allergen deposition and self-grooming behaviour by the host in response to the pruritis caused by the mites triggers the subsequent activation of a cutaneous inflammatory response [7] including an exudate which supplies the mite with a food source [8]. The skin lesions are induced by mite-derived pro-inflammatory factors, a likely source of which, are the mite excretory/secretory products, including potent enzymes and allergens (reviewed in [8]). While several mite products have been identified, including a number of enzymes and homologues of allergens of the house dust mite (HDM), Dermatophagoides pteronyssinus[10]
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