Infectious diseases represent a major threat for the sustainable development of fish farming. Efficient vaccines are not available against all diseases, and growing antibiotics resistance limits the use of antimicrobial drugs in aquaculture. It is therefore important to understand the basis of fish natural resistance to infections to help genetic selection and to develop new approaches against infectious diseases. However, the identification of the main mechanisms determining the resistance or susceptibility of a host to a pathogenic microbe is challenging, integrating the complexity of the variation of host genetics, the variability of pathogens, and their capacity of fast evolution and adaptation. Multiple approaches have been used for this purpose: (i) genetic approaches, QTL (quantitative trait loci) mapping or GWAS (genome-wide association study) analysis, to dissect the genetic architecture of disease resistance, and (ii) transcriptomics and functional assays to link the genetic constitution of a fish to the molecular mechanisms involved in its interactions with pathogens. To date, many studies in a wide range of fish species have investigated the genetic determinism of resistance to many diseases using QTL mapping or GWAS analyses. A few of these studies pointed mainly toward adaptive mechanisms of resistance/susceptibility to infections; others pointed toward innate or intrinsic mechanisms. However, in the majority of studies, underlying mechanisms remain unknown. By comparing gene expression profiles between resistant and susceptible genetic backgrounds, transcriptomics studies have contributed to build a framework of gene pathways determining fish responsiveness to a number of pathogens. Adding functional assays to expression and genetic approaches has led to a better understanding of resistance mechanisms in some cases. The development of knock-out approaches will complement these analyses and help to validate putative candidate genes critical for resistance to infections. In this review, we highlight fish isogenic lines as a unique biological material to unravel the complexity of host response to different pathogens. In the future, combining multiple approaches will lead to a better understanding of the dynamics of interaction between the pathogen and the host immune response, and contribute to the identification of potential targets of selection for improved resistance.

传染病对养鱼业的可持续发展构成重大威胁。并非针对所有疾病的有效疫苗，对抗生素的耐药性不断提高限制了水产养殖中抗菌药物的使用。因此，重要的是要了解鱼类对感染天然抵抗力的基础，以帮助基因选择和开发新的方法来应对传染病。然而，确定决定宿主对病原微生物的抗性或敏感性的主要机制是具有挑战性的，将宿主遗传学变异的复杂性，病原体的变异性及其快速进化和适应能力整合在一起。为此，使用了多种方法：（i）遗传方法，QTL（定量性状基因座）作图或GWAS（全基因组关联研究）分析，以剖析抗病性的遗传结构，以及（ii）转录组学和功能测定法，将鱼的遗传构成与其所涉及的分子机制联系起来与病原体的相互作用。迄今为止，许多鱼类的研究都使用QTL作图或GWAS分析研究了对许多疾病的抗性的遗传决定论。这些研究中的一些主要指向针对感染的抗性/敏感性的适应性机制。其他人则指出先天或内在机制。但是，在大多数研究中，潜在的机制仍然未知。通过比较抗性和易感遗传背景之间的基因表达谱，转录组学研究有助于建立确定鱼类对多种病原体反应能力的基因途径框架。在表达和遗传方法中增加功能性检测方法可以更好地理解耐药性机制。敲除方法的发展将对这些分析进行补充，并有助于验证对于抵抗感染至关重要的推定候选基因。在这篇综述中，我们着重介绍鱼类同基因系作为独特的生物材料，以阐明宿主对不同病原体反应的复杂性。将来，多种方法的结合将使人们更好地了解病原体与宿主免疫反应之间的相互作用动力学，并有助于确定潜在的选择目标以提高抗药性。