Mice Housed at Elevated Vivarium Temperatures Display Enhanced T-cell Response and Survival to Francisella tularensis

The inability to translate findings from studies performed in mouse models to the corresponding human condition is well known, especially those involving infectious, atherosclerotic, and other inflammatory diseases. We hypothesize that mice fail to a mount robust or adequate immune response to infectious agents because of physiologic effects of cold stress due to housing temperatures below the mouse thermoneutral zone (TNZ). This hypothesis was tested by comparing the immune response to the Francisella tularensis live vaccine strain in mice housed at a typical vivarium temperature, which is below the TNZ, with that of mice housed at a temperature near their TNZ. Mice maintained at 28 °C displayed elevated antigen-specific T-cell responses compared with mice housed at 22 °C and survived intranasal challenge that was fatal to immunized mice at 22 °C. These results demonstrate that cold stress due to housing below the mouse TNZ results in a blunted immune response and may compromise their translational value a models for infectious diseases and vaccine development.