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Distinct immune and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2022-04-18 , DOI: 10.1016/j.bbi.2022.04.015
Won Lee 1 , Tyler M Milewski 2 , Madeleine F Dwortz 3 , Rebecca L Young 4 , Andrew D Gaudet 5 , Laura K Fonken 6 , Frances A Champagne 2 , James P Curley 2
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Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. In particular, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift immune profiles and peripheral gene expression to match their contextual needs.



中文翻译:

小鼠社会等级中占主导地位的雄性和从属雄性的不同免疫和转录组学特征

社会地位是决定人类和非人类社会物种健康结果的关键因素。在具有生殖倾斜的社会等级制度中,个体竞争垄断资源并增加交配机会。这可能会带来巨大的能量成本,导致不同生理系统之间的权衡。特别是,对免疫系统的能量投资的变化可能对健康和健康产生重大的短期和长期影响。我们之前发现,生活在社会等级制度中的占主导地位的阿尔法雄性小鼠增加了与领土防御相关的代谢需求。在这项研究中,我们检验了以下假设,即高级雄性小鼠有利于获得性免疫,而低级小鼠则表现出对先天免疫的更高投入。我们在社会住房系统中安置了 12 组 10 只远交 CD-1 雄性小鼠。所有形成的线性社会等级和下属小鼠的血浆皮质酮 (CORT) 浓度高于阿尔法雄性。这种差异在高度专制的等级制度中更加突出。使用流式细胞术,我们发现优势状态与免疫表型向有利于适应性免疫和先天免疫的显着转变有关。使用 Tag-Seq 分析 alpha 和从属男性的肝脏和脾脏转录组,我们确定了调节与状态和/或 CORT 浓度相关的代谢和免疫防御途径的基因。在肝脏中,优势动物表现出相对较高的参与主要泌尿生产和分解代谢过程的特定基因的表达,而从属动物表现出相对较高的促进生物合成过程、伤口愈合、和促炎反应。在脾脏中,从属小鼠表现出相对较高的促进氧化磷酸化和 DNA 修复的基因表达,CORT 与参与淋巴细胞增殖和活化的基因呈负相关。总之,我们的研究结果表明,优势和从属动物适应性地改变免疫谱和外周基因表达以匹配其背景需求。

更新日期:2022-04-22
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