an immune-mediated protection against colitis along with improved colonic function. Our preliminary data led us to focus our efforts in this proposal on the specific mechanisms by which enteric infection alters gut function. The proposed studies contain 3 specific aims that are designed to test the following two central hypotheses: 1) infection-induced development and duration of changes in gut function are mediated by direct effects of cytokines on structural cells and on the interaction between structural and immune cells (Specific Aims 1 and 2);and 2) members of the IL-17 cytokine family are important in regulation of the functional effects associated with the Th1 or Th2 profiles (Specific Aim 3). The proposed approach will use mice infected with natural rodent pathogens, in vivo and in vitro studies of mucosal and smooth muscle function, primary cultures of immune cells, and molecular and immunohistochemical analyses. These studies will help us to understand how the host exploits physiological mechanisms in its defense against pathogens that allow for the stereotypic functional responses that promote expulsion. The impact of these studies is evident in that dysregulation of these functional changes significantly impairs host resistance and the maintenance of adequate barrier function and nutrient absorption. These studies also will provide insight on the mechanisms involved in the ability of nematode infection to protect against the development of autoimmune diseases, many of which are characterized by impaired intestinal barrier function. Project Description Page 6
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