Department of Biosciences, Centre for Ecological and Evolutionary Synthesis (CEES), University of Oslo, Oslo, Norway.
Department of Biosciences, Centre for Ecological and Evolutionary Synthesis (CEES), University of Oslo, Oslo, Norway.
Comp Biochem Physiol Part D Genomics Proteomics. 2019 Jun;30:333-346. doi: 10.1016/j.cbd.2019.04.004. Epub 2019 Apr 13.
The genetic repertoire underlying teleost immunity has been shown to be highly variable. A rare example is Atlantic cod and its relatives Gadiformes that lacks a hallmark of vertebrate immunity: Major Histocompatibility Complex class II. No immunological studies so far have fully unraveled the functionality of this particular immune system. Through global transcriptomic profiling, we investigate the immune response and host-pathogen interaction of Atlantic cod infected with the facultative intracellular bacterium Francisella noatunensis. We find that Atlantic cod displays an overall classic innate immune response with inflammation, acute-phase proteins and cell recruitment through up-regulation of e.g. IL1B, fibrinogen, cathelicidin, hepcidin and several chemotactic cytokines such as the neutrophil attractants CXCL1 and CXCL8. In terms of adaptive immunity, we observe up-regulation of interferon gamma followed by up-regulation of several MHCI transcripts and genes related to antigen transport and loading. Finally, we find up-regulation of immunoglobulins and down-regulation of T-cell and NK-like cell markers. Our analyses also uncover some contradictory transcriptional findings such as up-regulation of anti-inflammatory IL10 as well as down-regulation of the NADPH oxidase complex and myeloperoxidase. This we interpret as the result of host-pathogen interactions where F. noatunensis modulates the immune response. In summary, our results suggest that Atlantic cod mounts a classic innate immune response as well as a neutrophil-driven response. In terms of adaptive immunity, both endogenous and exogenous antigens are being presented on MHCI and antibody production is likely enabled through direct B-cell stimulation with possible neutrophil help. Collectively, we have obtained novel insight in the orchestration of the Atlantic cod immune system and determined likely targets of F. noatunensis host-pathogen interactions.
鱼类免疫的遗传基础具有高度的可变性。一个罕见的例子是大西洋鳕鱼及其近亲鲱形目鱼类，它们缺乏脊椎动物免疫的一个标志：主要组织相容性复合体 II 类。迄今为止，没有免疫学研究完全阐明这种特殊免疫系统的功能。通过全球转录组谱分析，我们研究了感染兼性细胞内细菌弗朗西斯氏菌的大西洋鳕鱼的免疫反应和宿主-病原体相互作用。我们发现大西洋鳕鱼表现出一种整体的经典先天免疫反应，伴有炎症、急性期蛋白和细胞募集，这是通过例如白细胞介素 1B、纤维蛋白原、抗菌肽、铁调素和几种趋化细胞因子（如中性粒细胞趋化因子 CXCL1 和 CXCL8）的上调来实现的。在适应性免疫方面，我们观察到干扰素 γ 的上调，随后是几种 MHC I 转录本和与抗原运输和加载相关的基因的上调。最后，我们发现免疫球蛋白的上调和 T 细胞和 NK 样细胞标记物的下调。我们的分析还揭示了一些矛盾的转录发现，例如抗炎性白细胞介素 10 的上调以及 NADPH 氧化酶复合物和髓过氧化物酶的下调。我们将其解释为宿主-病原体相互作用的结果，其中弗朗西斯氏菌调节免疫反应。总之，我们的结果表明，大西洋鳕鱼会引发经典的先天免疫反应和中性粒细胞驱动的反应。在适应性免疫方面，内源性和外源性抗原都在 MHC I 上呈递，并且通过可能的中性粒细胞辅助，直接 B 细胞刺激可能会导致抗体产生。总的来说，我们获得了关于大西洋鳕鱼免疫系统协调的新见解，并确定了弗朗西斯氏菌宿主-病原体相互作用的可能靶点。
