Cellular Mediator of Thermoregulatory Responses

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Mast cells are complex immune cells containing many mediators, though they are best known for their role in allergies (produce histamine) and peripheral inflammation (swelling and redness after a bug bite). Surprisingly, mast cells are found in the brain, and the number of brain mast cells increase under specific normal and pathological conditions. Their location in the brain, near blood vessels, suggests that mast cells are poised to regulate behavioral and physiological responses, including body temperature regulation. Pilot work suggests that blocking mast cell activation can alter the elevated temperature response caused by a pathogen entering the body. We have generated mast cell deficient mice to explore the necessity of these cells for a physiologically appropriate immune response. Experiments involve injecting lipopolysaccharide (a piece of a bacteria cell) and measuring the resulting responses (i.e. body temperature, locomotor activity). This injection acts as a stimulus for mounting the immune system, causing a fever in normal mice, just like the reaction to bacteria. Three experimental groups will be studied: normal, mast cell deficient, and age matched adult deficient mice in which the mast cells have been reconstituted. The mast cell deficient mice are predicted to show little to no temperature change following injection of bacterial cell wall, while the response should be restored to normal in the reconstituted animals. Follow-up studies will explore how mast cells contribute to fever. The discovery that mast cells participate in thermoregulation would represent a revolutionizing instance of immune cells impacting physiology and behavior. In addition, the contribution of mast cells in the brain could change the current thinking that the brain is an immune-privileged site and further support the notion that non-neuronal cells in the brain contribute to the control of behavior. This project willprovide unique training opportunities for undergraduate and graduate students in the lab.