Department of Psychology, University of Texas at Austin, Austin, TX, USA; Department of In Vivo Pharmacology Services, The Jackson Laboratory, Sacramento, CA, USA.
Department of Psychology, University of Texas at Austin, Austin, TX, USA.
Brain Behav Immun. 2022 Jul;103:130-144. doi: 10.1016/j.bbi.2022.04.015. Epub 2022 Apr 18.
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.
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。在具有生殖偏斜的社会等级制度中，个体竞争以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，免疫系统的能量投资变化会对适应度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优势阿尔法雄性老鼠会增加与领土防御相关的代谢需求。在这项研究中，我们测试了一个假设，即高等级雄性老鼠更喜欢适应性免疫，而从属老鼠在先天免疫方面的投资更高。我们将 12 组 10 只杂交 CD-1 雄性老鼠饲养在一个社会饲养系统中。所有老鼠都形成了线性社会等级制度，从属老鼠的血浆皮质酮（CORT）浓度比阿尔法雄性老鼠高。在高度专制的等级制度中，这种差异更为明显。使用流式细胞术，我们发现优势地位与免疫表型向有利于适应性免疫而非先天免疫的显著转变有关。使用 Tag-Seq 对阿尔法和从属雄性的肝脏和脾脏转录组进行分析，我们鉴定出了调节代谢和免疫防御途径的基因，这些基因与地位和/或 CORT 浓度有关。在肝脏中，优势动物表现出特定基因的相对较高表达，这些基因涉及主要尿液产生和分解代谢过程，而从属动物则表现出相对较高表达的基因，这些基因促进合成代谢过程、伤口愈合和促炎反应。在脾脏中，从属老鼠表现出相对较高表达的基因，这些基因有利于氧化磷酸化和 DNA 修复，而 CORT 与涉及淋巴细胞增殖和激活的基因呈负相关。总之，我们的研究结果表明，优势和从属动物会自适应地改变免疫特征和外周基因表达，以适应其环境需求。
