Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis

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.

Host Transcription Factors in the Immediate Pro-Inflammatory Response to the Parasitic Mite Psoroptes ovis

“…A similar result was also described by Hammad et al, [63]. We recently confirmed the findings of previous studies which identified the presence of a P. ovis homologue of Der p 2 (termed Pso o 2) which, like Der p 2, contains a conserved MD-2-related lipid-recognition (ML) domain and has 41% amino acid identity with Der p 2 [11], [64], [65]. Pso o 2 also maintains a number of important features deemed to be necessary for MD-2 like activity, including six conserved cysteine residues, N-glycosylation sites and conserved lysine residues involved in binding LPS [60], [61], [66].…”

“…The triggering of this rapid and extensive inflammatory response by mite-derived factors is clearly of central interest in elucidating the initiation of the immunopathology associated with sheep scab. A previous study by our group demonstrated that expression of key members of the TLR4-signalling pathway including TLR4, MYD88 and CD14 where all up-regulated in sheep skin within a few hours of exposure to P. ovis , thus implicating an LPS-type response resulting in the activation of NF-kB and AP-1 [11]. The triggering of innate immune receptors by parasites is not novel, for example the parasitic nematode Acanthocheilonema viteae (via the ES62 molecule) and the parasitic trematode Schistosoma mansoni [via lacto-N-fucopentaose III (LNFPIII)] have been shown to induce NF-kB-mediated immune responses by activating the TLR4-signalling pathway [58], [59].…”

Generation, analysis and functional annotation of expressed sequence tags from the ectoparasitic mite Psoroptes ovis

“…HDM Der p 3 allergen is a 30 kDa serine protease with trypsin-like activity that is able to enzymatically digest the complement components C3 and C5, generating the anaphylatoxins C3a and C5a, thus contributing to the pathogenesis of allergic disease [41]. We have previously demonstrated the involvement of the complement system in the host response to P. ovis [6] and the identification of a Der p 3 homologue in P. ovis adds further support to this finding. The identification of a Der p 21 homologue is a significant finding and could indicate a novel mechanism by which P. ovis interacts with the host immune response.…”

Preliminary analysis of Psoroptes ovis transcriptome in different developmental stages

“…Mites abrade the cuticle and deposit allergens when establishing themselves on the host, that results in severe inflammatory responses [13, 14] and the production of an exudate that, in turn, represents a food source for the mites [15]. Features of psoroptic mange include intense pruritus, extensive dermatitis, depilation and hyperkeratosis, which ultimately result in emaciation or death caused by secondary bacterial infections.…”