Moredun Research Institute, Pentlands Science Park, Edinburgh, Scotland, United Kingdom.
PLoS One. 2011;6(9):e24402. doi: 10.1371/journal.pone.0024402. Epub 2011 Sep 7.
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. 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.
Through 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.
Interrogation 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.
绵羊疥癣是由寄生性外寄生虫螨 Psoroptes ovis 引起的，导致皮肤炎症迅速发展，并导致疾病特有的结痂皮肤损伤。我们之前描述了全球宿主对 P. ovis 感染的转录反应，阐明了导致快速而深刻的免疫反应的炎症过程的要素。然而，引发这种反应的机制尚不清楚。为了确定新的干预方法，更好地了解引发免疫反应的早期事件至关重要。本研究的目的是更清楚地了解引发即刻促炎反应的机制和信号通路。
通过转录因子结合位点富集和途径分析的结合，我们确定了许多转录因子在引发皮肤炎症中的关键作用。特别是，转录因子 NF-kB 和 AP-1 在早期促炎反应的协调中发挥了明确的作用，这些因子参与了一系列炎症介质的激活。
对宿主对 P. ovis 感染的时间反应的探究进一步确定了引发即刻宿主促炎反应的机制。这种反应涉及转录因子 NF-kB 和 AP-1 的关键调节作用。途径分析表明，这些转录因子的激活可能是在宿主 LPS 样反应后触发的，可能涉及 TLR4 信号转导，也可能存在这种情况的有趣可能性，即这可能是由 P. ovis 过敏原引发的。
