The immune system is a highly complex, multi-facetted system that is the body's most effective defense against infection and similar challenges. The mast cell (MC) is a species of immune system cell whose functions have been to a large extent unclear. Two recent discoveries about MC, however, have opened new perspectives on their roles. First, it has been shown that MC deficiency compromises the host defense to severe infections to such an extent that mortality is dramatically increased Thus, MC are necessary for effective host defense to some pathogens. Second, it has been shown that various types of stimuli can elicit the migration of MC from the periphery into the brain parenchyma. The demonstration of this migration strongly indicates that they serve an important function in bran mediated immune system responses. The goal of the experiments proposed in this application is to extend the understanding of brain MC in what is perhaps the most ubiquitous brain-mediated immune response, the acute phase response (APR). The APR includes a number of behaviors, including anorexia, adipsia, and lethargy, as well as fever that are elicited by stimulation of the innate immune system by infection, neoplasm, sterile irritation and other stimuli. Thus, we propose a detailed analysis of the role of MC in the APR and of some of the MC involvement in APR, to examine mechanisms mediating this response and to bridge behavioral knowledge of the APR elements with molecular mechanisms by which it is produced.
