RCUK-CONICYT Mucosal health and microbiota during sea lice parasitism: effect of oral delivery of immunomodulants

鱼的粘膜表面（皮肤、肠和鳃）不断与各种病原体相互作用，与常驻粘膜微生物群不协调，是宿主防御的第一道防线。几种免疫因子已被描述在鱼粘液中，它们的存在和丰度可受到病原体感染的影响。因此，粘膜相关的微生物群可能受到影响，这可能导致生态失调，体内或体内的微生物失衡，这降低了微生物群对先天免疫系统的有益作用，并可能导致机会微生物的继发感染。海虱（鲑虱（Lepeophtheirus salmonis）和Caligus spp.）感染是世界范围内海洋养殖鲑鱼疾病的最经济重要的病原体。Caligus rogercresseyi是影响智利鲑鱼产业的主要体外寄生虫，估计每年的成本高达1.2亿美元。这种寄生虫破坏了为继发性感染病原体提供入口的体壁的外表面，并且受感染的鱼也变得紧张，这导致免疫抑制，从而增加了对继发性感染的易感性。其他卡里吉斯寄生虫（Caligus rogercresseyi和其他Caligus spp.）对世界上发展中国家和发达国家的海水养殖业都有不利影响，每年造成1亿美元的经济损失。因此，开发新的方法来预防或减少海虱感染是该行业的高度优先事项。改善治疗策略的一个必要前提是更好地了解宿主-微生物组-寄生虫之间在表皮界面的关系。因此，这项研究计划的目的是评估海虱寄生对粘膜健康的影响，包括免疫反应和宿主微生物群的方面。我们将评估免疫调节剂对海虱感染易感性的影响，并通过测定表皮粘液蛋白质组反应、微生物群变化和粘膜转录组变化来评估免疫调节剂对肠道和粘液质量的影响。我们将在寄生的早期阶段将宿主和海虱的反应联系起来，以开发新的策略（即识别疫苗抗原，RNAi靶点，益生菌，益生元，免疫调节剂）用于海冰控制。

The mucosal surfaces (skin, intestine and gills) of fish are constantly interacting with a wide range of pathogens and, inconcert with the resident mucosal microbiota, are the first line of host defence. Several immune factors have beendescribed in fish mucus and their presence and abundance can be affected by pathogen infection. As a consequence, themucosa-associated microbiota can be affected and this may lead to dysbiosis, a microbial imbalance on or inside the body,which reduces the beneficial role of microbiota on the innate immune system and may lead to secondary infections byopportunistic microbes. Sea lice (Lepeophtheirus salmonis and Caligus spp.) infections are the most economicallyimportant causative agents of disease in marine-farmed salmonids worldwide. Caligus rogercresseyi is the mainectoparasite affecting the Chilean salmon industry with estimated costs of up to $120 million annually. This parasitedamages external surfaces of the integument providing portal of entry for secondary infectious pathogens, and infected fishalso become stressed which leads to immunosuppression with consequent increased susceptibility to the secondaryinfections. Other Caligid parasites (Caligus rogercresseyi and other Caligus spp.) have detrimental impacts on mariculture operations in both developing and developed parts of the world which causes economic losses of US$ 100's millionsannually. The development of novel methods to prevent or reduce sea lice infection is therefore a high priority for theindustry. An essential prerequisite for improved treatments strategies is a better understanding of relationship betweenhost-microbiome-parasite at the epidermal interface. Therefore, the aim of this research programme is to evaluate theinfluence of sea lice parasitism on mucosal health, including aspects of the immune response and host microbiota. We willevaluate the effect of immunomodulants on susceptibility to sea lice infection, and on gut and mucus quality by determiningepidermal mucus proteomic responses, microbiota changes and mucosal transcriptomic changes. We will correlate theresponses of the host and the sea lice during the early stages of parasitism in order to develop new strategies (i.e. identifyantigens for vaccines, targets for RNAi, probiotics, prebiotics, immunomodulants) for sea ice control.