The mechanism(s) involved in the intestinal tract response to S. typhimurium infection is not completely understood. We have recently shown that the interaction(s) of stem cell factor (SCF) with its receptor, c-kit, may be important in the intestinal tract response to S. typhimurium infection. The overall goal of this proposal is to test the following hypothesis: The production of SCF and its subsequent interaction(s) with its receptor, c-kit, are important events in the intestinal tract response to S. typhimurium infection. To test this hypothesis, we will address the following Specific Aims: 1) Determine the role(s) of SCF production and c-kit/SCF-positive cells in the susceptibility of mice to oral Salmonella challenge. 2) Determine if SCF:c-kit interaction(s) play an important role in the in vivo production of IFN( and/or TNF-( following Salmonella infection. 3) Characterize the cells in the intestinal tract and/or gut-associated lymphoid tissue which are producing elevated levels of SCF and/or c-kit following in vivo challenge with S. typhimurium. To address the above aims, we have proposed experiments to answer the following questions: 1) Do intestinal intraepithelial lymphocytes (IEL), and/or IEL-mast cell interactions play a role in the enhanced susceptibility of WWv mice to oral Salmonella challenge? 2) Can in vivo SCF supplementation of S1/S1d mice or normal mice alter their respective susceptibilities to oral Salmonella challenge? 3) Do normal mice treated in vivo with SCF or antibody to SCF and/or c-kit have altered intestinal tract or mucosal-associated lymphoid tissues in response to Salmonella infection, and if so, does bone marrow transplantation and/or in vivo SCF supplementation change such altered cytokine production? The results from these studies will be important for future development of vaccines which use Salmonella, and for further understanding the role of SCF plays in the pathophysiology associated with enteric bacterial infections.
| Ramarathinam, L; Niesel, D W; Klimpel, G R (1993) Ity influences the production of IFN-gamma by murine splenocytes stimulated in vitro with Salmonella typhimurium. J Immunol 150:3965-72 |
| Ramarathinam, L; Niesel, D W; Klimpel, G R (1993) Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. J Immunol 150:3973-81 |
