Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems
Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems
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DOI：
10.1242/jeb.173146
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发表时间：
2018-07-01
影响因子：
2.8
通讯作者：
Macqueen, Daniel J.
中科院分区：
文献类型：
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作者：
Alzaid, Abdullah;Kim, Jin-Hyoung;Macqueen, Daniel J.
在感染过程中抑制生长可能有助于资源分配，以实现有效的免疫功能。过去的工作支持这一假设在鲑鱼揭示了免疫反应调节胰岛素样生长因子（IGF）系统-生长激素（GH）下游的内分泌途径。骨骼肌是鱼类生长和能量储存的主要目标，但对其生长在免疫反应期间如何调节知之甚少。我们解决了这一知识差距，肌肉免疫反应的大小匹配的银鲑（Oncorhynchus kisutch）实现不同的增长速度。我们比较了一个野生型菌株与两个GH转基因组从相同的遗传背景实现最大或抑制生长-一个设计分离生长激素的直接影响，其对生长速度和营养状态的影响。在注射后30 h，用磷酸盐缓冲盐水（对照）或细菌或病毒感染的模拟物对鱼进行取样。我们定量了GH、GH受体、IGF激素、IGF 1受体和IGF结合蛋白家族基因的mRNA表达水平，沿着的还有参与炎症或抗病毒反应的免疫基因和肌肉生长状态标记基因。我们证明，与野生型相比，GH转基因动物的免疫功能受到抑制。实现快速生长的GH转基因动物的肌肉没有表现出可检测到的抗病毒反应，加上组成性炎症状态的证据。GH和IGF系统基因表达强烈改变GH转基因和快速生长，无论是基线表达和免疫刺激的反应。因此，GH转基因强烈破坏肌肉免疫状态和正常的GH和IGF系统对免疫刺激的表达反应。
Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system - an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterising muscle immune responses in size-matched coho salmon (Oncorhynchus kisutch) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth - a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30 h post-injection with phosphate-buffered saline (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared with wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation.