Distinct inflammatory and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies

Abstract

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. Particularly, 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 energetically inexpensive 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 an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation 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 energy investment in immune functioning and gene expression to match their contextual energetic demands.

Female behavior drives the formation of distinct social structures in C57BL/6J versus wild-derived outbred mice in field enclosures

“…Though in low complexity environments or at high densities males may form dominance hierarchies 19,25 . The formation and consequences of dominance hierarchies among male mice have been the subject of recent study in the lab 19,77,85 , though our results suggest that when given ample and defensible spaces male mice will tend to avoid interacting with others and form individual territories rather than a dominance hierarchy. The flexibility of house mouse social structure under different conditions has undoubtedly been important for their ecological success across diverse commensal and natural environments 20,23,86,87 .…”

“…Previous studies of wild mouse behavior have reported males will defend territories and attempt to monopolize spaces and exclude other males 25,29 and our data show this behavior is retained in male lab mice. The formation and consequences of dominance hierarchies among male mice have been the subject of recent study in the lab 19,92,107 , but our results suggest that when given ample and defensible spaces male mice will tend to avoid interacting with others and form individual territories rather than a single integrated dominance hierarchy. Differences between territoriality and dominance behaviors remain poorly understood at the mechanistic level.…”