Effects of pair-housing pubertal and adult male and female mice on LPS-induced age-dependent immune responses: A potential role for the gut microbiota

Puberty is a critical period of development that is marked by the maturation of the stress and immune systems. There are marked age and sex differences in peripheral and central inflammatory responses to an immune challenge between pubertal and adult mice. Given the strong link between the gut microbiome and immune system, it is possible that the age and sex differences in immune responses are mediated by age and sex differences in gut microbial composition. The current study investigated whether cohousing adult and pubertal CD1 mice through three weeks of pair-housing, with the potential for microbiome exchange via coprophagy and other close contact, could mitigate age-dependent immune responses. Cytokine concentrations in the blood and cytokine mRNA expression in the brain were assessed following exposure to the immune challenge lipopolysaccharide (LPS). The results show that all mice displayed increased cytokine concentrations in serum and central cytokine mRNA expression in the hippocampus, hypothalamus and prefrontal cortex (PFC) at eight hours following LPS treatment. Pubertal male and female mice, that were pair-housed with a pubertal counterpart, displayed lower cytokine concentrations in serum and lower cytokine mRNA expression in the brain compared to adult mice that were pair-housed with an adult counterpart. However, when adult and pubertal mice were pair-housed, the age differences in both peripheral cytokine concentrations and central cytokine mRNA expression were mitigated. We also found that pair-housing adult and pubertal mice eliminated the age difference in gut bacterial diversity. These results suggest that microbial composition could be involved in modulating these age-associated immune responses and thus may represent a potential therapeutic target.