Abstract

Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of “sickness behaviors.” Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To do this, we used remote tracking of social interactions of a wild population of house mice (Mus musculus domesticus) to categorize animals in terms of gregariousness. Blood, hair, brain and other tissue samples from animals with extreme gregariousness phenotypes were collected. We then tested whether the levels of three important cytokines (TNF-α, IFN-γ and IL-1β) in the serum, cortex and hypothalamus of these animals could be explained by the gregariousness phenotype and/or sex of the mice. Using the hair as a long-term quantification of steroid hormones, we also tested whether corticosterone, progesterone and testosterone differed by social phenotype. We found main effects of gregariousness and sex on the serum levels of TNF-α, but not on IFN-γ or IL-1β. Brain gene expression levels were not different between phenotypes. All hair steroids tended to be elevated in animals of high gregariousness phenotype, independent of sex. In sum, elements of the immune system may be associated with gregariousness, even outside of major disease events. These results extend our knowledge of the role that immune signals have in contributing to the regulation of social behaviors outside periods of illness.

Highlights

  • One of the most powerful ways to alter the social behavior of animals is to make them sick

  • Studies in mice have shown that social interactions alter proinflammatory cytokine gene expression in the hypothalamus of endotoxin injected males (Weil et al, 2006)

  • We focused on two brain areas, the hypothalamus and the prefrontal cortex, that are important for social interactions (Ko, 2017) and where cytokine production has been shown to occur (Rothwell and Luheshi, 2000; Vitkovic et al, 2000; Monteiro et al, 2017)

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Summary

Introduction

One of the most powerful ways to alter the social behavior of animals is to make them sick. Immunity and Gregariousness production and release of proinflammatory cytokines (Dantzer, 2017). This peripheral message reaches the brain in multiple ways and activates neural responses, including the local production of cytokines (Dantzer, 2017). Given the extensive set of effects that proinflammatory cytokines can have on the behavior of sick animals, it is not surprising that links between inflammation and social dysfunction have been uncovered. Targeted deletion of the IFNγ receptor in prefrontal cortex neurons was sufficient to alter social behavior, leading to a lack of social preference, highlighting involvement of IFN-γ signaling in the brain in the maintenance of normal social behavior

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