Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization

Free-living mammals, such as humans and wild mice, display heightened immune activation compared with artificially maintained laboratory mice. These differences are partially attributed to microbial exposure as laboratory mice infected with pathogens exhibit immune profiles more closely resembling that of free-living animals. Here, we examine how colonization by microorganisms within the natural environment contributes to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. However, these “rewilded” mice were not infected by pathogens previously implicated in immune activation. Rather, immune system changes were associated with altered microbiota composition with notable increases in intestinal fungi. Fungi isolated from rewilded mice were sufficient in increasing circulating granulocytes. These findings establish a model to investigate how the natural environment impacts immune development and show that sustained fungal exposure impacts granulocyte numbers. [Display omitted] •Controlled release of lab mice into the wild alters the state of the immune system•Rewilded mice harbor an altered microbiota including increases in intestinal fungi•Fungi from rewilded mice induce granulocyte expansion in laboratory mice Laboratory mice are maintained in artificial conditions that potentially impact immunity. In this issue of Cell Host & Microbe, Yeung et al. (2020) demonstrate that mice released into a wild enclosure display increases in circulating granulocytes that are associated with an altered microbiota, notably expansion of fungi.