Sex-dependent responses in mice to a natural microbial environment 4174

Abstract Description Rationale Lab mice, although not germ-free, lack normal exposures to diverse commensal and environmental microorganisms. Dirty mice, as those found in the wild or in pet stores are referred to, have diverse microbiomes and history of infection with multiple pathogens; their immune systems mirror those of adult humans. It is possible to turn lab mice dirty by co-housing C57BL/6, or other genetically inbred mouse strains, with pet store mice or their dirty bedding. Due to concerns regarding aggression, dirty mouse studies typically only include female mice; if they do include male mice, they are co-housed with dirty bedding only. Methods We used divided rat cages to co-house C57BL/6J mice of both sexes for 8 weeks with either pet store mice or their dirty bedding before assessing pathogen transfer and immune profiles of brain and spleen. Results Live co-housing resulted in increased pathogen transfer and sex-dependent immune changes in brain and spleen compared to clean mice or dirty bedding alone. Co-housed males became ill later and more severely than females, showing active infection after 8 weeks while the illnesses of females had resolved. Conclusions These findings suggest that co-housing method is important in determining the changes that occur as lab mice get dirty. The sex-dependent nature of these changes suggests female-only dirty mouse studies are insufficient in representing the altered immunology of these immune-appropriate mouse models. Funding Sources Supported by Mayo Clinic Graduate School of Biomedical Sciences Topic Categories Mucosal and Regional Immunology (MUC)