Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout
Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout
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DOI：
10.1210/en.2015-2024
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发表时间：
2016-05-01
期刊：
影响因子：
4.8
通讯作者：
Martin, Samuel A. M.
中科院分区：
文献类型：
--
作者：
Alzaid, Abdullah;Castro, Rosario;Martin, Samuel A. M.
虽然疾病和感染与生长减弱有关，但所涉及的分子途径的特征很差。我们推测，IGF轴，脊椎动物生长的中央总督，在感染过程中受到抑制，以促进资源重新分配向免疫。这一假设进行了测试虹鳟鱼（虹鳟鱼）的挑战，杀鲑气单胞菌（AS），革兰氏阴性细菌病原体，或病毒性出血性败血症病毒（VHSV）在孵化，第一次喂养，和第一次喂养后3周。对编码IGF激素、19种鲑鱼IGF结合蛋白（IGFBPs）和一组生长和免疫状态标记基因的基因进行定量转录谱分析。IGF轴对AS和VHSv的发育反应存在重大差异，VHSv的攻击导致许多基因的强烈下调。尽管如此，IGFBP-1A 1和IGFBP-6A 2亚型，每一个IGF信号负调节剂，高度诱导AS和VHSv与宿主防御基因的细胞因子途径调节的惊人的相关性。后续实验表明，一个非常显着的协同调节IGFBP-1A 1和IGFBP-6A 2与促炎细胞因子基因在初级免疫组织（脾和头肾）时，鳟鱼的挑战，由不同的革兰氏阴性菌，鲁氏耶尔森氏菌。基于我们的研究结果，我们提出了一种模型，其中某些IGFBP亚型直接受细胞因子信号通路的调节，允许根据免疫激活水平立即调节生长和/或免疫系统表型。我们的研究结果提供了新的和全面的见解之间的串扰保守的途径调节硬骨鱼的生长，发育和免疫力。
Although disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterized. We postulated that the IGF axis, a central governor of vertebrate growth, is repressed during infection to promote resource reallocation towards immunity. This hypothesis was tested in rainbow trout (Oncorhynchus mykiss) challenged by Aeromonas salmonicida (AS), a Gram-negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding, and 3 weeks after first feeding. Quantitative transcriptional profiling was performed for genes encoding both IGF hormones, 19 salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong down-regulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes, each negative regulators of IGF signaling, were highly induced by AS and VHSv in striking correlation with host defense genes regulated by cytokine pathways. Follow-up experiments demonstrated a highly significant coregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative bacterium, Yersinia ruckeri. Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signaling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our findings provide new and comprehensive insights into cross talk between conserved pathways regulating teleost growth, development, and immunity.