Immune-Endocrine Links to Gregariousness in Wild House Mice

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.

Wild mice with different social network sizes vary in brain gene expression

“…Sample sizes were 7 for females of each type (large or small) of social network size, and 7 and 8 for males with large and small social network sizes, respectively. Average social network size was not different between the sexes for the sampled animals [90]. Estimated age (in days) of sampled animals did not significantly differ by sex or social network size type (large or small) and was 207.2 ± 57.7 and 246.6 ± 68.1 for females and males with large social networks, respectively, and 250 ± 63.2 and 125.8 ± 45.6, for females and males with small social networks, respectively [90].…”

“…For the current study, we analyzed brain gene expression from house mice whose tissues had been previously used in a study aimed at identifying relationships between immune system functioning and social behavior [ 90 ]. Those animals were captured during the non-reproductive season (winter months), which reduces the presence of untagged individuals (pups or subadults below 18 g), as well as any confounding effects due to reproductive activity.…”

“…Average social network size was not different between the sexes for the sampled animals [ 90 ]. Estimated age (in days) of sampled animals did not significantly differ by sex or social network size type (large or small) and was 207.2 ± 57.7 and 246.6 ± 68.1 for females and males with large social networks, respectively, and 250 ± 63.2 and 125.8 ± 45.6, for females and males with small social networks, respectively [ 90 ]. Body mass was obtained using a Sartorius scale (BL1500S) and differences in body mass due to sex, social network size or an interaction of the two terms, were tested using a two-way anova in R. As the RFID-logging system also allowed us to track how much time animals spent in nest boxes and how often they went in and out of boxes, we used these metrics to assess whether time spent in nest boxes or activity (going in and out of nest boxes) explained variation in the social network size trait.…”

“…Surgical micropunches (EMS Rapid Core Instruments) were used to dissect the brain regions of interest from 100 μm slices, which were spaced out by two 20 μm slices that were collected for histochemistry onto microscope slides (Fisherbrand, item 12–550-15). We collected punches for the prefrontal cortex, the hypothalamus and the entire hippocampus following the coordinates described in [ 90 ] based on the Allen Mouse Brain Atlas: P56, Coronal Reference Atlas [ 94 ]. We focused on these brain regions because they include nuclei important for social decision making and social memory [ 14 , 95 ].…”

“…Also, during this season, mice in our population spend a considerable amount of time (up to 19 h per day) inside of the nest boxes [89]; therefore, we consider the number of partners encountered in nest boxes during this time as a good proxy of their social network size. Animals with extreme social network sizes were selected based on being consistently (over 3 separate non-consecutive days during the week prior to capture) approximately either 1 standard deviation (STD) above (large social network size) or below (small social network size) the mean egocentric social network size for the entire population (mean ± STD: 26 ± 8.6 partners/day) [90]. Social network size is defined here as the total number of different individuals encountered in nest boxes per day; in social network literature, this value (number of ties) is referred to as degree or egocentric network size [91].…”