Understanding the relationship between gill disease and immune status

鱼类是蛋白质和欧米茄-3脂肪酸的主要来源。随着世界范围内渔业的下降，鱼类养殖业增加，以填补差距，目前供应约一半的鱼类消费。生产必须继续增加，以供应日益增长的人口。大西洋鲑鱼养殖业是苏格兰的一个重大成功故事，苏格兰是全球第三大大西洋鲑鱼生产国，也是农村地区的主要雇主。水产养殖业的可持续性依赖于对鱼类健康的良好管理和对疾病的有效控制。在苏格兰鲑鱼养殖中，控制海虱和改善鳃健康是目前该部门面临的两个最重要的健康问题。鳃的健康影响鱼类在海上的表现，需要昂贵的，往往效果不佳的治疗。缺乏信息的主机（鲑鱼）在不同的疾病状态下的鳃的反应已被强调在最近的几个行业主导的研讨会在苏格兰。因此，本申请提出通过使用来自过去研究的存档样品，对暴露于引起阿米巴鳃病（AGD）的主要鳃寄生虫后在鳃中表达的基因进行深入研究来解决该问题。我们将确定鳃，作为一个多功能的器官，负责氧气的吸收，呼吸调节，以及在一个主要的病原体进入点的防御，是否有一个有限的范围内作出反应，在鱼的病原体。我们将重点阐明伤口愈合途径激活和生长因子可能释放，导致组织重塑，因为许多鳃疾病引起类似的病理，在板层融合和上皮细胞增生。来自该初步研究的数据也将用于鉴定与鳃健康相关的候选生物标志物，以用于进一步研究。接下来，我们将对各种鳃疾病状态下的生物标志物进行qPCR分析。我们的合作者将在2017/18年夏末/秋季收集养殖鱼类的鳃样本，当时鳃病最流行。最初，将对鳃样本进行病原体筛选，以确认导致病理学的物种以及是否涉及单一或合并感染。生物标志物分析将揭示在不同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，以改善鳃健康，抵御多种疾病。最后，我们将尝试使用不同的免疫调节剂调节鳃的反应，以确定这种方法是否可以改善鳃健康/疾病保护。我们将集中在管理的4分子，我们知道是有效的诱导剂的促炎途径或抗病毒防御。它们将包括鞭毛蛋白、poly I：C和两种细胞因子（IL-1 β和IFN-γ，来自一种相关的鲑鱼虹鳟鱼），这些细胞因子在我们实验室中可以作为重组蛋白质随时使用，也可以购买（poly I：C）。给药后，我们将在一段时间内对鳃组织进行采样，并检查对该计划早期确定的生物标志物以及已知的抗菌和抗病毒途径的影响。鳃反应的最佳调节剂将由我们的工业合作者在鲑鱼现场进行试验，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.