Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, Midlothian, EH26 0PZ, Scotland, UK.
BMC Genomics. 2010 Nov 10;11:624. doi: 10.1186/1471-2164-11-624.
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. 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.
Infestation 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.
This 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.
绵羊皮肤感染外寄生虫痒螨（Psoroptes ovis）会导致迅速的皮肤免疫反应，导致结痂皮肤病变，这是绵羊疥癣的特征。对于这种深刻的炎症反应是如何引发的，以及为了识别新的疫苗和药物靶点，我们知之甚少，因此更好地了解宿主-寄生虫关系是至关重要的。本研究的主要目的是对感染痒螨后体内皮肤反应进行联合网络和途径分析，以更清楚地了解所涉及的机制和信号通路。
感染痒螨在 24 小时时间过程中导致 1552 个基因的差异表达。通过峰基因表达聚类，可以将基因分类为具有时间相关性的分组。聚类的网络和途径分析确定了宿主对感染反应涉及的关键信号通路。分析表明，许多基因在过敏和炎症中具有作用，包括促炎细胞因子（IL1A、IL1B、IL6、IL8 和 TNF）以及参与免疫细胞激活和募集的因子（SELE、SELL、SELPH、ICAM1、CSF2、CSF3、CCL2 和 CXCL2）。该分析还强调了转录因子 NF-kB 和 AP-1 在早期促炎反应中的影响，并表明存在向 Th2 型免疫反应的偏向。
本研究为绵羊疥癣中导致促炎反应发展的信号机制提供了新的见解，同时提供了有关可能触发这种反应的螨虫因子的本质的重要信息。它使我们能够阐明暴露于痒螨后免疫系统调节的时间模式，为病变发展的机制提供了新的见解。本研究提高了我们对宿主对痒螨的反应的现有认识，包括确定绵羊疥癣与其他炎症性皮肤疾病之间的关键相似之处，以及确定疾病控制的潜在靶点。
