Abstract
The immune systems of free-living mammals such as humans and wild mice display a heightened degree of activation compared with laboratory mice maintained under artificial conditions. Here, we demonstrate that releasing inbred laboratory mice into an outdoor enclosure to mimic life in a natural environment alters the state of immunity. In addition to enhancing the differentiation of T cell populations previously associated with pathogen exposure, we found that outdoor release of mice led to an increase in circulating granulocytes. However, rewilded mice were not infected by pathogens previously implicated in immune activation. Rather, changes to the immune system were associated with an altered composition of the microbiota, and fungi isolated from rewilded mice were sufficient to increase granulocytes. These findings establish an experimental procedure to investigate the impact of the natural environment on immune development and identify a role for sustained fungal colonization in determining granulocyte numbers.
One sentence summary Controlled release of laboratory mice into a natural environment changes the composition of the bacterial and fungal microbiota leading to an altered immune system.
