Currently there is a disagreement among investigators on whether pathogenic salmonellae do survive and multiply within host phagocytes. In the present proposal, murine salmonellosis is used as the experimental model to resolve this controversy by: (a) confirmation of the present preliminary observations showing the sequential destruction of Salmonella typhimurium within peritoneal exudate cells of mice, as visualized under electron microscopy; and (b) identification of the precise location(s) in host tissues of the reticuloendothelial system (i.e., within phagocytes or parenchymal cells and/or in the extracellular space) where bacterial multiplication occurs, employing a combination of electron microscopy, Giemsa-stained tissue sections and immunofluorescent and immunoperoxidase techniques. This project is considered as a crucial step in the understanding of host defense mechanism and of acquired immunity in salmonellosis. Such a definitive observation will facilitate the elucidation of the mechanisms of protective immunity induced by salmonella vaccines.
