Understanding the relationship between gill disease and immune status

鱼是蛋白质和omega-3脂肪酸的主要来源。随着全球渔业的下降，渔业养殖业已经增加，以填补这一缺口，目前供应了大约一半的鱼类消费。生产必须继续增加，才能满足日益增长的人口的需求。大西洋三文鱼养殖业一直是苏格兰的一个主要成功故事，苏格兰是全球第三大大西洋三文鱼生产国，也是农村地区的主要雇主。水产养殖业的可持续性取决于对鱼类健康的良好管理和对疾病的有效控制。在苏格兰鲑鱼养殖业中，控制海虱和改善鳃健康是该部门目前面临的两个最重要的健康问题。鳃健康对鱼类在海上的表现产生影响，以及需要昂贵且往往效果不佳的治疗方法。最近在苏格兰举行的几个行业主导的研讨会上，强调了不同疾病州宿主(三文鱼)对鳃反应的信息不足。因此，本申请建议通过使用过去研究中的存档样本，对暴露于引起阿米巴腮病(AGD)的主要鳃寄生虫后，在鳃中表达的基因进行深入研究，以解决这一问题。我们将确定鳃作为一个多功能器官，负责摄氧量、渗透调节以及病原体主要入口点的防御，对鱼类中的病原体是否有有限的反应范围。我们将重点阐明激活的伤口愈合途径和可能释放的导致组织重塑的生长因子，因为许多鳃疾病在板层融合和上皮细胞增殖方面会引起类似的病理变化。这项初步研究的数据还将用于识别与鳃健康相关的候选生物标记物，用于进一步研究。接下来，我们将对不同鳃疾病状态下的生物标记物进行qPCR分析。我们的合作者将在2017/18年夏末/秋季采集养殖鱼类的鳃样本，这是鳃疾病最流行的时候。最初，将对鳃样本进行病原体筛选，以确认引起病理的物种，以及是否涉及单一或联合感染。生物标志物分析将揭示在不同的疾病状态下是否存在共同的途径，从而有可能改变这些途径，以改善鳃对多种疾病的健康。最后，我们将尝试使用不同的免疫调节剂来调节鳃的反应，以确定这种方法是否可以改善鳃健康/疾病保护。我们将重点介绍对4种分子的管理，我们知道这些分子是促炎途径或抗病毒防御的有效诱导者。它们将包括鞭毛蛋白、PolyI：C和两种细胞因子(IL-1β和干扰素-γ，来自一种相关的鲑鱼-彩虹鲑鱼)，它们可以作为重组蛋白在我们的实验室获得，即可使用，或可以购买(PolyI：C)。在给药后，我们将在一段时间内对鳃组织进行采样，并检查对计划早些时候确定的生物标记物以及已知的抗微生物和抗病毒途径的影响。我们的工业合作伙伴将在鲑鱼现场试验最好的鳃反应调节剂，以评估对鳃健康的影响。

Fish are a major source of protein and omega-3 fatty acids. With the decline in fisheries worldwide, fish farming has increased to fill the gap and currently supplies around half of all fish consumed. Production must continue to increase in order to supply the increasing human population. The Atlantic salmon farming industry has been a major success story in Scotland, the third largest producer of Atlantic salmon globally, and is a major employer in rural areas. The sustainability of the aquaculture industry relies on good management of fish health and effective control of diseases. Within Scottish salmon farming, control of sea lice and improvement of gill health are currently the two most important health issues that the sector faces. Gill health impacts on the performance of fish at sea, and the need for expensive and often poorly efficacious therapeutic treatments. Lack of information of host (salmon) responses in gills in different disease states has been highlighted at several recent industry-led workshops in Scotland. Therefore this application proposes to address this issue by undertaking an in-depth study of the genes expressed in gills following exposure to a major gill parasite that causes amoebic gill disease (AGD), using archived samples from a past study. We will determine whether the gill, as a multifunctional organ responsible for oxygen uptake, osmoregulation, as well as defence at a major point of entry for pathogens, has a limited scope to react to pathogens in fish. We will focus on elucidating the wound healing pathways activated and the growth factors potentially released that cause tissue remodelling, since many gill diseases cause similar pathologies, in terms of lamellar fusion and epithelial cell hyperplasia. The data from this initial study will also be used to identify candidate biomarkers relevant for gill health, to be used for further studyNext we will undertake qPCR analysis of the biomarkers in a variety of gill disease states. Gill samples from farmed fish will be collected during the late summer/autumn of 2017/18 by our collaborators, when gill disease is most prevalent. Initially the gill samples will be screened for pathogen presence to confirm the species causing the pathology and whether single or co-infections are involved. The biomarker analysis will reveal if common pathways are seen in different disease states, allowing the potential to alter these pathways to improve gill health against multiple diseases.Lastly, we will try to modulate the gill responses using different immunomodulators to establish if this approach can improve gill health/ disease protection. We will focus on administration of a 4 molecules that we know are potent inducers of pro-inflammatory pathways or anti-viral defences. They will include flagellin, poly I:C and two cytokines (IL-1beta and IFN-gamma, from a related salmonid the rainbow trout) that are available in our lab as recombinant protein ready for use, or can be purchased (poly I:C). Following administration we will sample gill tissue over a time course and examine the impact on the biomarkers identified earlier in the programme, as well as on known antimicrobial and anti-viral pathways. The best modulator of gill responses will be trialled on a salmon site by our industrial collaborator to assess the impact on gill health.